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Current Medicinal Chemistry

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ISSN (Online): 1875-533X

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Review Article

Sulfated Non-Saccharide Glycosaminoglycan Mimetics as Novel Drug Discovery Platform for Various Pathologies

Author(s): Daniel K. Afosah and Rami A. Al-Horani*

Volume 27, Issue 21, 2020

Page: [3412 - 3447] Pages: 36

DOI: 10.2174/0929867325666181120101147

Price: $65

Abstract

Glycosaminoglycans (GAGs) are very complex, natural anionic polysaccharides. They are polymers of repeating disaccharide units of uronic acid and hexosamine residues. Owing to their template-free, spatiotemporally-controlled, and enzyme-mediated biosyntheses, GAGs possess enormous polydispersity, heterogeneity, and structural diversity which often translate into multiple biological roles. It is well documented that GAGs contribute to physiological and pathological processes by binding to proteins including serine proteases, serpins, chemokines, growth factors, and microbial proteins. Despite advances in the GAG field, the GAG-protein interface remains largely unexploited by drug discovery programs. Thus, Non-Saccharide Glycosaminoglycan Mimetics (NSGMs) have been rationally developed as a novel class of sulfated molecules that modulate GAG-protein interface to promote various biological outcomes of substantial benefit to human health. In this review, we describe the chemical, biochemical, and pharmacological aspects of recently reported NSGMs and highlight their therapeutic potentials as structurally and mechanistically novel anti-coagulants, anti-cancer agents, anti-emphysema agents, and anti-viral agents. We also describe the challenges that complicate their advancement and describe ongoing efforts to overcome these challenges with the aim of advancing the novel platform of NSGMs to clinical use.

Keywords: Glycosaminoglycans, sulfated molecules, non-saccharide glycosaminoglycan mimetics, anticoagulants, anticancer, antivirals.

« Previous Next »
[1]
Gandhi, N.S.; Mancera, R.L. The structure of glycosaminoglycans and their interactions with proteins. Chem. Biol. Drug Des., 2008, 72(6), 455-482.
[http://dx.doi.org/10.1111/j.1747-0285.2008.00741.x] [PMID: 19090915]
[2]
Esko, J.D.; Kimata, K.; Lindahl, U. Proteoglycans and Sulfated Glycosaminoglycans in: Essentials of Glycobiology; Varki, A.; Cummings, R.D.; Esko, J.D.; Freeze, H.H.; Hart, G.W.; Etzler, M.E. (Eds.). Cold Spring Harbor Laboratory Press, 2009, p. 784.
[PMID: 20301236]
[3]
Imberty, A.; Lortat-Jacob, H.; Pérez, S. Structural view of glycosaminoglycan-protein interactions. Carbohydr. Res., 2007, 342(3-4), 430-439.
[http://dx.doi.org/10.1016/j.carres.2006.12.019] [PMID: 17229412]
[4]
Pomin, V.H.; Mulloy, B. Glycosaminoglycans and Proteoglycans. Pharmaceuticals (Basel), 2018, 11(1), 27.
[http://dx.doi.org/10.3390/ph11010027] [PMID: 29495527]
[5]
Sasisekharan, R.; Venkataraman, G. Heparin and heparan sulfate: biosynthesis, structure and function. Curr. Opin. Chem. Biol., 2000, 4(6), 626-631.
[http://dx.doi.org/10.1016/S1367-5931(00)00145-9] [PMID: 11102866]
[6]
Capila, I.; Linhardt, R.J. Heparin-protein interactions. Angew. Chem. Int. Ed. Engl., 2002, 41(3), 391-412.
[http://dx.doi.org/10.1002/1521-3773(20020201)41:3<390:: AID-ANIE390>3.0.CO;2-B] [PMID: 12491369]
[7]
Mulloy, B.; Hogwood, J.; Gray, E.; Lever, R.; Page, C.P. Pharmacology of heparin and related drugs. Pharmacol. Rev., 2016, 68(1), 76-141.
[http://dx.doi.org/10.1124/pr.115.011247] [PMID: 26672027]
[8]
Mizumoto, S.; Yamada, S.; Sugahara, K. Molecular interactions between chondroitin-dermatan sulfate and growth factors/receptors/matrix proteins. Curr. Opin. Struct. Biol., 2015, 34, 35-42.
[http://dx.doi.org/10.1016/j.sbi.2015.06.004] [PMID: 26164146]
[9]
Monslow, J.; Govindaraju, P.; Puré, E. Hyaluronan - a functional and structural sweet spot in the tissue microenvironment. Front. Immunol., 2015, 6, 231.
[http://dx.doi.org/10.3389/fimmu.2015.00231] [PMID: 26029216]
[10]
Caterson, B.; Melrose, J. Keratan sulfate, a complex glycosaminoglycan with unique functional capability. Glycobiology, 2018, 28(4), 182-206.
[http://dx.doi.org/10.1093/glycob/cwy003] [PMID: 29340594]
[11]
Bourin, M.C.; Lindahl, U. Glycosaminoglycans and the regulation of blood coagulation. Biochem. J., 1993, 289(Pt 2), 313-330.
[http://dx.doi.org/10.1042/bj2890313] [PMID: 8380990]
[12]
Rabenstein, D.L. Heparin and heparan sulfate: structure and function. Nat. Prod. Rep., 2002, 19(3), 312-331.
[http://dx.doi.org/10.1039/b100916h] [PMID: 12137280]
[13]
Ruoslahti, E.; Yamaguchi, Y. Proteoglycans as modulators of growth factor activities. Cell, 1991, 64(5), 867-869.
[http://dx.doi.org/10.1016/0092-8674(91)90308-L] [PMID: 2001586]
[14]
Sasisekharan, R.; Shriver, Z.; Venkataraman, G.; Narayanasami, U. Roles of heparan-sulphate glycosaminoglycans in cancer. Nat. Rev. Cancer, 2002, 2(7), 521-528.
[http://dx.doi.org/10.1038/nrc842] [PMID: 12094238]
[15]
Yip, G.W.; Smollich, M.; Götte, M. Therapeutic value of glycosaminoglycans in cancer. Mol. Cancer Ther., 2006, 5(9), 2139-2148.
[http://dx.doi.org/10.1158/1535-7163.MCT-06-0082] [PMID: 16985046]
[16]
Lever, R.; Smailbegovic, A.; Page, C. Role of glycosaminoglycans in inflammation. Inflammopharmacology, 2001, 9, 165-169.
[http://dx.doi.org/10.1163/156856001300248443]
[17]
Gozzo, A.J.; Nunes, V.A.; Carmona, A.K.; Nader, H.B.; von Dietrich, C.P.; Silveira, V.L.; Shimamoto, K.; Ura, N.; Sampaio, M.U.; Sampaio, C.A.; Araújo, M.S. Glycosaminoglycans affect the action of human plasma kallikrein on kininogen hydrolysis and inflammation. Int. Immunopharmacol., 2002, 2(13-14), 1861-1865.
[http://dx.doi.org/10.1016/S1567-5769(02)00145-5] [PMID: 12489800]
[18]
Holzmann, J.; Brandl, N.; Zemann, A.; Schabus, R.; Marlovits, S.; Cowburn, R.; Huettinger, M. Assorted effects of TGFbeta and chondroitinsulfate on p38 and ERK1/2 activation levels in human articular chondrocytes stimulated with LPS. Osteoarthritis Cartilage, 2006, 14(6), 519-525.
[http://dx.doi.org/10.1016/j.joca.2005.12.005] [PMID: 16503173]
[19]
Yasuda, T. Hyaluronan inhibits cytokine production by lipopolysaccharide-stimulated U937 macrophages through down-regulation of NF-kappaB via ICAM-1. Inflamm. Res., 2007, 56(6), 246-253.
[http://dx.doi.org/10.1007/s00011-007-6168-5] [PMID: 17607549]
[20]
Nelson, R.M.; Cecconi, O.; Roberts, W.G.; Aruffo, A.; Linhardt, R.J.; Bevilacqua, M.P. Heparin oligosaccharides bind L- and P-selectin and inhibit acute inflammation. Blood, 1993, 82(11), 3253-3258.
[http://dx.doi.org/10.1182/blood.V82.11.3253.3253] [PMID: 7694675]
[21]
Jinno, A.; Park, P.W. Role of glycosaminoglycans in infectious disease. Methods Mol. Biol., 2015, 1229, 567-585.
[http://dx.doi.org/10.1007/978-1-4939-1714-3_45] [PMID: 25325982]
[22]
Aquino, R.S.; Park, P.W. Glycosaminoglycans and infection. Front. Biosci., 2016, 21, 1260-1277.
[http://dx.doi.org/10.2741/4455] [PMID: 27100505]
[23]
Tiwari, V.; O’donnell, C.; Copeland, R.J.; Scarlett, T.; Liu, J.; Shukla, D. Soluble 3-O-sulfated heparan sulfate can trigger herpes simplex virus type 1 entry into resistant Chinese hamster ovary (CHO-K1) cells. J. Gen. Virol., 2007, 88(Pt 4), 1075-1079.
[http://dx.doi.org/10.1099/vir.0.82476-0] [PMID: 17374750]
[24]
Choudhary, S.; Marquez, M.; Alencastro, F.; Spors, F.; Zhao, Y.; Tiwari, V. Herpes simplex virus type-1 (HSV-1) entry into human mesenchymal stem cells is heavily dependent on heparan sulfate. J. Biomed. Biotechnol., 2011, 2011, 264350
[http://dx.doi.org/10.1155/2011/264350] [PMID: 21799659]
[25]
Witvrouw, M.; De Clercq, E. Sulfated polysaccharides extracted from sea algae as potential antiviral drugs. Gen. Pharmacol., 1997, 29(4), 497-511.
[http://dx.doi.org/10.1016/S0306-3623(96)00563-0] [PMID: 9352294]
[26]
Kim, M.; Yim, J.H.; Kim, S.Y.; Kim, H.S.; Lee, W.G.; Kim, S.J.; Kang, P.S.; Lee, C.K. In vitro inhibition of influenza A virus infection by marine microalga-derived sulfated polysaccharide p-KG03. Antiviral Res., 2012, 93(2), 253-259.
[http://dx.doi.org/10.1016/j.antiviral.2011.12.006] [PMID: 22197247]
[27]
Volpi, N. Therapeutic applications of glycosaminoglycans. Curr. Med. Chem., 2006, 13(15), 1799-1810.
[http://dx.doi.org/10.2174/092986706777452470] [PMID: 16787222]
[28]
Zhang, L. Glycosaminoglycan (GAG) biosynthesis and GAG-binding proteins. Prog. Mol. Biol. Transl. Sci., 2010, 93, 1-17.
[http://dx.doi.org/10.1016/S1877-1173(10)93001-9] [PMID: 20807638]
[29]
Jackson, R.L.; Busch, S.J.; Cardin, A.D. Glycosaminoglycans: molecular properties, protein interactions, and role in physiological processes. Physiol. Rev., 1991, 71(2), 481-539.
[http://dx.doi.org/10.1152/physrev.1991.71.2.481] [PMID: 2006221]
[30]
Hileman, R.E.; Fromm, J.R.; Weiler, J.M.; Linhardt, R.J. Glycosaminoglycan-protein interactions: definition of consensus sites in glycosaminoglycan binding proteins. BioEssays , 1998, 20(2), 156-167.
[http://dx.doi.org/10.1002/(SICI)1521-1878(199802)20: 2<156::AID-BIES8>3.0.CO;2-R] [PMID: 9631661]
[31]
Fromm, J.R.; Hileman, R.E.; Caldwell, E.E.; Weiler, J.M.; Linhardt, R.J. Pattern and spacing of basic amino acids in heparin binding sites. Arch. Biochem. Biophys., 1997, 343(1), 92-100.
[http://dx.doi.org/10.1006/abbi.1997.0147] [PMID: 9210650]
[32]
Hileman, R.E.; Jennings, R.N.; Linhardt, R.J. Thermodynamic analysis of the heparin interaction with a basic cyclic peptide using isothermal titration calorimetry. Biochemistry, 1998, 37(43), 15231-15237.
[http://dx.doi.org/10.1021/bi980212x] [PMID: 9790687]
[33]
Fromm, J.R.; Hileman, R.E.; Caldwell, E.E.O.; Weiler, J.M.; Linhardt, R.J. Differences in the interaction of heparin with arginine and lysine and the importance of these basic amino acids in the binding of heparin to acidic fibroblast growth factor. Arch. Biochem. Biophys., 1995, 323(2), 279-287.
[http://dx.doi.org/10.1006/abbi.1995.9963] [PMID: 7487089]
[34]
McCoy, A.J.; Pei, X.Y.; Skinner, R.; Abrahams, J-P.; Carrell, R.W. Structure of beta-antithrombin and the effect of glycosylation on antithrombin’s heparin affinity and activity. J. Mol. Biol., 2003, 326(3), 823-833.
[http://dx.doi.org/10.1016/S0022-2836(02)01382-7] [PMID: 12581643]
[35]
Cardin, A.D.; Weintraub, H.J. Molecular modeling of protein-glycosaminoglycan interactions. Arteriosclerosis, 1989, 9(1), 21-32.
[http://dx.doi.org/10.1161/01.ATV.9.1.21] [PMID: 2463827]
[36]
Sobel, M.; Soler, D.F.; Kermode, J.C.; Harris, R.B. Localization and characterization of a heparin binding domain peptide of human von Willebrand factor. J. Biol. Chem., 1992, 267(13), 8857-8862.
[PMID: 1577724]
[37]
Margalit, H.; Fischer, N.; Ben-Sasson, S.A. Comparative analysis of structurally defined heparin binding sequences reveals a distinct spatial distribution of basic residues. J. Biol. Chem., 1993, 268(26), 19228-19231.
[PMID: 8366075]
[38]
Fath, M.A.; Wu, X.; Hileman, R.E.; Linhardt, R.J.; Kashem, M.A.; Nelson, R.M.; Wright, C.D.; Abraham, W.M. Interaction of secretory leukocyte protease inhibitor with heparin inhibits proteases involved in asthma. J. Biol. Chem., 1998, 273(22), 13563-13569.
[http://dx.doi.org/10.1074/jbc.273.22.13563] [PMID: 9593692]
[39]
Malik, A.; Ahmad, S. Sequence and structural features of carbohydrate binding in proteins and assessment of predictability using a neural network. BMC Struct. Biol., 2007, 7, 1.
[http://dx.doi.org/10.1186/1472-6807-7-1] [PMID: 17201922]
[40]
Pratt, C.W.; Church, F.C. General features of the heparin-binding serpins antithrombin, heparin cofactor II and protein C inhibitor. Blood Coagul. Fibrinolysis, 1993, 4(3), 479-490.
[http://dx.doi.org/10.1097/00001721-199306000-00013] [PMID: 8392392]
[41]
Al-Horani, R.A. Serpin regulation of fibrinolytic system: implications for therapeutic applications in cardiovascular diseases. Cardiovasc. Hematol. Agents Med. Chem., 2014, 12(2), 91-125.
[http://dx.doi.org/10.2174/1871525712666141106095927] [PMID: 25374013]
[42]
Gettins, P.G.W. Serpin structure, mechanism, and function. Chem. Rev., 2002, 102(12), 4751-4804.
[http://dx.doi.org/10.1021/cr010170+] [PMID: 12475206]
[43]
Huntington, J.A.; Read, R.J.; Carrell, R.W. Structure of a serpin-protease complex shows inhibition by deformation. Nature, 2000, 407(6806), 923-926.
[http://dx.doi.org/10.1038/35038119] [PMID: 11057674]
[44]
Desai, U.R. New antithrombin-based anticoagulants. Med. Res. Rev., 2004, 24(2), 151-181.
[http://dx.doi.org/10.1002/med.10058] [PMID: 14705167]
[45]
Desai, U.R.; Petitou, M.; Björk, I.; Olson, S.T. Mechanism of heparin activation of antithrombin: evidence for an induced-fit model of allosteric activation involving two interaction subsites. Biochemistry, 1998, 37(37), 13033-13041.
[http://dx.doi.org/10.1021/bi981426h] [PMID: 9737884]
[46]
Olson, S.T.; Richard, B.; Izaguirre, G.; Schedin-Weiss, S.; Gettins, P.G. Molecular mechanisms of antithrombin-heparin regulation of blood clotting proteinases. A paradigm for understanding proteinase regulation by serpin family protein proteinase inhibitors. Biochimie, 2010, 92(11), 1587-1596.
[http://dx.doi.org/10.1016/j.biochi.2010.05.011] [PMID: 20685328]
[47]
Choay, J.; Petitou, M.; Lormeau, J.C.; Sinaÿ, P.; Casu, B.; Gatti, G. Structure-activity relationship in heparin: a synthetic pentasaccharide with high affinity for antithrombin III and eliciting high anti-factor Xa activity. Biochem. Biophys. Res. Commun., 1983, 116(2), 492-499.
[http://dx.doi.org/10.1016/0006-291X(83)90550-8] [PMID: 6651824]
[48]
Lane, D.A.; Denton, J.; Flynn, A.M.; Thunberg, L.; Lindahl, U. Anticoagulant activities of heparin oligosaccharides and their neutralization by platelet factor 4. Biochem. J., 1984, 218(3), 725-732.
[http://dx.doi.org/10.1042/bj2180725] [PMID: 6721831]
[49]
Johnson, D.J.; Li, W.; Adams, T.E.; Huntington, J.A. Antithrombin-S195A factor Xa-heparin structure reveals the allosteric mechanism of antithrombin activation. EMBO J., 2006, 25(9), 2029-2037.
[http://dx.doi.org/10.1038/sj.emboj.7601089] [PMID: 16619025]
[50]
Li, W.; Johnson, D.J.; Esmon, C.T.; Huntington, J.A. Structure of the antithrombin-thrombin-heparin ternary complex reveals the antithrombotic mechanism of heparin. Nat. Struct. Mol. Biol., 2004, 11(9), 857-862.
[http://dx.doi.org/10.1038/nsmb811] [PMID: 15311269]
[51]
Nordenman, B.; Danielsson, A.; Björk, I. The binding of low-affinity and high-affinity heparin to antithrombin. Fluorescence studies. Eur. J. Biochem., 1978, 90(1), 1-6.
[http://dx.doi.org/10.1111/j.1432-1033.1978.tb12567.x] [PMID: 710412]
[52]
Weitz, J.I.; Young, E.; Johnston, M.; Stafford, A.R.; Fredenburgh, J.C.; Hirsh, J. Vasoflux, a new anticoagulant with a novel mechanism of action. Circulation, 1999, 99(5), 682-689.
[http://dx.doi.org/10.1161/01.CIR.99.5.682] [PMID: 9950667]
[53]
Olson, S.T.; Björk, I.; Sheffer, R.; Craig, P.A.; Shore, J.D.; Choay, J. Role of the antithrombin-binding pentasaccharide in heparin acceleration of antithrombin-proteinase reactions. Resolution of the antithrombin conformational change contribution to heparin rate enhancement. J. Biol. Chem., 1992, 267(18), 12528-12538.
[PMID: 1618758]
[54]
Turk, B.; Brieditis, I.; Bock, S.C.; Olson, S.T.; Björk, I. The oligosaccharide side chain on Asn-135 of alpha-antithrombin, absent in beta-antithrombin, decreases the heparin affinity of the inhibitor by affecting the heparin-induced conformational change. Biochemistry, 1997, 36(22), 6682-6691.
[http://dx.doi.org/10.1021/bi9702492] [PMID: 9184148]
[55]
Verhamme, I.M.; Bock, P.E.; Jackson, C.M. The preferred pathway of glycosaminoglycan-accelerated inactivation of thrombin by heparin cofactor II. J. Biol. Chem., 2004, 279(11), 9785-9795.
[http://dx.doi.org/10.1074/jbc.M313962200] [PMID: 14701814]
[56]
Petitou, M.; Casu, B.; Lindahl, U. 1976-1983, a critical period in the history of heparin: the discovery of the antithrombin binding site. Biochimie, 2003, 85(1-2), 83-89.
[http://dx.doi.org/10.1016/S0300-9084(03)00078-6] [PMID: 12765778]
[57]
Ersdal-Badju, E.; Lu, A.; Zuo, Y.; Picard, V.; Bock, S.C. Identification of the antithrombin III heparin binding site. J. Biol. Chem., 1997, 272(31), 19393-19400.
[http://dx.doi.org/10.1074/jbc.272.31.19393] [PMID: 9235938]
[58]
Jin, L.; Abrahams, J.P.; Skinner, R.; Petitou, M.; Pike, R.N.; Carrell, R.W. The anticoagulant activation of antithrombin by heparin. Proc. Natl. Acad. Sci. USA, 1997, 94(26), 14683-14688.
[http://dx.doi.org/10.1073/pnas.94.26.14683] [PMID: 9405673]
[59]
Arocas, V.; Turk, B.; Bock, S.C.; Olson, S.T.; Björk, I. The region of antithrombin interacting with full-length heparin chains outside the high-affinity pentasaccharide sequence extends to Lys136 but not to Lys139. Biochemistry, 2000, 39(29), 8512-8518.
[http://dx.doi.org/10.1021/bi9928243] [PMID: 10913257]
[60]
Tollefsen, D.M.; Pestka, C.A.; Monafo, W.J. Activation of heparin cofactor II by dermatan sulfate. J. Biol. Chem., 1983, 258(11), 6713-6716.
[PMID: 6687888]
[61]
Gunnarsson, G.T.; Desai, U.R. Designing small, nonsugar activators of antithrombin using hydropathic interaction analyses. J. Med. Chem., 2002, 45(6), 1233-1243.
[http://dx.doi.org/10.1021/jm020012q] [PMID: 11881992]
[62]
Gunnarsson, G.T.; Desai, U.R. Interaction of designed sulfated flavanoids with antithrombin: lessons on the design of organic activators. J. Med. Chem., 2002, 45(20), 4460-4470.
[http://dx.doi.org/10.1021/jm020132y] [PMID: 12238925]
[63]
Gunnarsson, G.T.; Desai, U.R. Exploring new non-sugar sulfated molecules as activators of antithrombin. Bioorg. Med. Chem. Lett., 2003, 13(4), 679-683.
[http://dx.doi.org/10.1016/S0960-894X(02)01055-7] [PMID: 12639557]
[64]
Gunnarsson, G.T.; Riaz, M.; Adams, J.; Desai, U.R. Synthesis of per-sulfated flavonoids using 2,2,2-trichloro ethyl protecting group and their factor Xa inhibition potential. Bioorg. Med. Chem., 2005, 13(5), 1783-1789.
[http://dx.doi.org/10.1016/j.bmc.2004.11.060] [PMID: 15698795]
[65]
Gunnarsson, G.T.; Desai, U.R. Hydropathic interaction analyses of small organic activators binding to antithrombin. Bioorg. Med. Chem., 2004, 12(3), 633-640.
[http://dx.doi.org/10.1016/j.bmc.2003.10.034] [PMID: 14738974]
[66]
Raghuraman, A.; Liang, A.; Krishnasamy, C.; Lauck, T.; Gunnarsson, G.T.; Desai, U.R. On designing non-saccharide, allosteric activators of antithrombin. Eur. J. Med. Chem., 2009, 44(6), 2626-2631.
[http://dx.doi.org/10.1016/j.ejmech.2008.09.042] [PMID: 18996625]
[67]
Liang, A.; Raghuraman, A.; Desai, U.R. Capillary electrophoretic study of small, highly sulfated, non-sugar molecules interacting with antithrombin. Electrophoresis, 2009, 30(9), 1544-1551.
[http://dx.doi.org/10.1002/elps.200800642] [PMID: 19425011]
[68]
Al-Horani, R.A.; Liang, A.; Desai, U.R. Designing nonsaccharide, allosteric activators of antithrombin for accelerated inhibition of factor Xa. J. Med. Chem., 2011, 54(17), 6125-6138.
[http://dx.doi.org/10.1021/jm2008387] [PMID: 21800826]
[69]
Di Cera, E. Serine proteases. IUBMB Life, 2009, 61(5), 510-515.
[http://dx.doi.org/10.1002/iub.186] [PMID: 19180666]
[70]
Hedstrom, L. Serine protease mechanism and specificity. Chem. Rev., 2002, 102(12), 4501-4524.
[http://dx.doi.org/10.1021/cr000033x] [PMID: 12475199]
[71]
Al-Horani, R.A.; Afosah, D.K. Recent advances in the discovery and development of factor XI/XIa inhibitors. Med. Res. Rev., 2018, 38(6), 1974-2023.
[http://dx.doi.org/10.1002/med.21503] [PMID: 29727017]
[72]
Al-Horani, R.A.; Desai, U.R. Recent advances on plasmin inhibitors for the treatment of fibrinolysis-related disorders. Med. Res. Rev., 2014, 34(6), 1168-1216.
[http://dx.doi.org/10.1002/med.21315] [PMID: 24659483]
[73]
Tuder, R.M.; Voelkel, N.F. Pathobiology of emphysema. Chronic obstructive lung diseases 2008, 2, 63-75.
[74]
Sabroe, I.; Parker, L.C.; Calverley, P.M.; Dower, S.K.; Whyte, M.K. Pathological networking: a new approach to understanding COPD. Postgrad. Med. J., 2008, 84(991), 259-264.
[http://dx.doi.org/10.1136/thx.2007.077768] [PMID: 18508983]
[75]
Fischer, B.M.; Pavlisko, E.; Voynow, J.A. Pathogenic triad in COPD: oxidative stress, protease-antiprotease imbalance, and inflammation. Int. J. Chron. Obstruct. Pulmon. Dis., 2011, 6, 413-421.
[http://dx.doi.org/10.2147/COPD.S10770] [PMID: 21857781]
[76]
Bock, P.E.; Panizzi, P.; Verhamme, I.M.A. Exosites in the substrate specificity of blood coagulation reactions. J. Thromb. Haemost., 2007, 5(Suppl. 1), 81-94.
[http://dx.doi.org/10.1111/j.1538-7836.2007.02496.x] [PMID: 17635714]
[77]
O’Brien, L.A.; Stafford, A.R.; Fredenburgh, J.C.; Weitz, J.I. Glycosaminoglycans bind factor Xa in a Ca2+-dependent fashion and modulate its catalytic activity. Biochemistry, 2003, 42(44), 13091-13098.
[http://dx.doi.org/10.1021/bi0345586] [PMID: 14596625]
[78]
Sheehan, J.P.; Sadler, J.E. Molecular mapping of the heparin-binding exosite of thrombin (antithrombin III/serine proteases). Biochemistry, 1994, 91, 5518-5522.
[79]
Badellino, K.O.; Walsh, P.N. Localization of a heparin binding site in the catalytic domain of factor XIa. Biochemistry, 2001, 40(25), 7569-7580.
[http://dx.doi.org/10.1021/bi0027433] [PMID: 11412111]
[80]
Gan, Z.R.; Li, Y.; Chen, Z.; Lewis, S.D.; Shafer, J.A. Identification of basic amino acid residues in thrombin essential for heparin-catalyzed inactivation by antithrombin III. J. Biol. Chem., 1994, 269(2), 1301-1305.
[PMID: 8288594]
[81]
Carter, W.J.; Cama, E.; Huntington, J.A. Crystal structure of thrombin bound to heparin. J. Biol. Chem., 2005, 280(4), 2745-2749.
[http://dx.doi.org/10.1074/jbc.M411606200] [PMID: 15548541]
[82]
Li, W.; Adams, T.E.; Nangalia, J.; Esmon, C.T.; Huntington, J.A. Molecular basis of thrombin recognition by protein C inhibitor revealed by the 1.6-A structure of the heparin-bridged complex. Proc. Natl. Acad. Sci. USA, 2008, 105(12), 4661-4666.
[http://dx.doi.org/10.1073/pnas.0711055105] [PMID: 18362344]
[83]
Rezaie, A.R. Identification of basic residues in the heparin-binding exosite of factor Xa critical for heparin and factor Va binding. J. Biol. Chem., 2000, 275(5), 3320-3327.
[http://dx.doi.org/10.1074/jbc.275.5.3320] [PMID: 10652320]
[84]
Zhao, M.; Abdel-Razek, T.; Sun, M.F.; Gailani, D. Characterization of a heparin binding site on the heavy chain of factor XI. J. Biol. Chem., 1998, 273(47), 31153-31159.
[http://dx.doi.org/10.1074/jbc.273.47.31153] [PMID: 9813019]
[85]
Ho, D.H.; Badellino, K.; Baglia, F.A.; Walsh, P.N. A binding site for heparin in the apple 3 domain of factor XI. J. Biol. Chem., 1998, 273(26), 16382-16390.
[http://dx.doi.org/10.1074/jbc.273.26.16382] [PMID: 9632702]
[86]
Chander, A.; Atkinson, H.M.; Stevic, I.; Berry, L.R.; Kim, P.Y.; Chan, A.K.C. Interactions of heparin and a covalently-linked antithrombin-heparin complex with components of the fibrinolytic system. Thromb. Haemost., 2013, 110(6), 1180-1188.
[http://dx.doi.org/10.1160/TH13-04-0290] [PMID: 24048327]
[87]
Bauer, P.I.; Pozsgay, M.; Machovich, R.; Elödi, P.; Horváth, I. The interaction of heparin with human plasmin. Int. J. Biochem., 1983, 15(6), 871-874.
[http://dx.doi.org/10.1016/0020-711X(83)90161-1] [PMID: 6222929]
[88]
Kostoulas, G.; Hörler, D.; Naggi, A.; Casu, B.; Baici, A. Electrostatic interactions between human leukocyte elastase and sulfated glycosaminoglycans: physiological implications. Biol. Chem., 1997, 378(12), 1481-1489.
[http://dx.doi.org/10.1515/bchm.1997.378.12.1481] [PMID: 9461347]
[89]
Volpi, N. Inhibition of human leukocyte elastase activity by chondroitin sulfates. Chem. Biol. Interact., 1997, 105(3), 157-167.
[http://dx.doi.org/10.1016/S0009-2797(97)00045-8] [PMID: 9291994]
[90]
Walsh, R.L.; Dillon, T.J.; Scicchitano, R.; McLennan, G. Heparin and heparan sulphate are inhibitors of human leucocyte elastase. Clin. Sci. (Lond.), 1991, 81(3), 341-346.
[http://dx.doi.org/10.1042/cs0810341] [PMID: 1655335]
[91]
Spencer, J.L.; Stone, P.J.; Nugent, M.A. New insights into the inhibition of human neutrophil elastase by heparin. Biochemistry, 2006, 45(30), 9104-9120.
[http://dx.doi.org/10.1021/bi060338r] [PMID: 16866356]
[92]
Verghese, J.; Liang, A.; Sidhu, P.P.; Hindle, M.; Zhou, Q.; Desai, U.R. First steps in the direction of synthetic, allosteric, direct inhibitors of thrombin and factor Xa. Bioorg. Med. Chem. Lett., 2009, 19(15), 4126-4129.
[http://dx.doi.org/10.1016/j.bmcl.2009.06.013] [PMID: 19540113]
[93]
Sidhu, P.S.; Liang, A.; Mehta, A.Y.; Abdel Aziz, M.H.; Zhou, Q.; Desai, U.R. Rational design of potent, small, synthetic allosteric inhibitors of thrombin. J. Med. Chem., 2011, 54(15), 5522-5531.
[http://dx.doi.org/10.1021/jm2005767] [PMID: 21714536]
[94]
Abdel Aziz, M.H.; Sidhu, P.S.; Liang, A.; Kim, J.Y.; Mosier, P.D.; Zhou, Q.; Farrell, D.H.; Desai, U.R. Designing allosteric regulators of thrombin. Monosulfated benzofuran dimers selectively interact with Arg173 of exosite 2 to induce inhibition. J. Med. Chem., 2012, 55(15), 6888-6897.
[http://dx.doi.org/10.1021/jm300670q] [PMID: 22788964]
[95]
Afosah, D.K.; Verespy, S., III; Al-Horani, R.A.; Boothello, R.S.; Karuturi, R.; Desai, U.R. A small group of sulfated benzofurans induces steady-state submaximal inhibition of thrombin. Bioorg. Med. Chem. Lett., 2018, 28(6), 1101-1105.
[http://dx.doi.org/10.1016/j.bmcl.2018.01.069] [PMID: 29459207]
[96]
Sidhu, P.S.; Abdel Aziz, M.H.; Sarkar, A.; Mehta, A.Y.; Zhou, Q.; Desai, U.R. Designing allosteric regulators of thrombin. Exosite 2 features multiple subsites that can be targeted by sulfated small molecules for inducing inhibition. J. Med. Chem., 2013, 56(12), 5059-5070.
[http://dx.doi.org/10.1021/jm400369q] [PMID: 23718540]
[97]
Verespy, S., III; Mehta, A.Y.; Afosah, D.; Al-Horani, R.A.; Desai, U.R. Allosteric partial inhibition of monomeric proteases. Sulfated coumarins induce regulation, not just inhibition, of thrombin. Sci. Rep., 2016, 6, 24043.
[http://dx.doi.org/10.1038/srep24043] [PMID: 27053426]
[98]
Al-Horani, R.A.; Ponnusamy, P.; Mehta, A.Y.; Gailani, D.; Desai, U.R. Sulfated pentagalloylglucoside is a potent, allosteric, and selective inhibitor of factor XIa. J. Med. Chem., 2013, 56(3), 867-878.
[http://dx.doi.org/10.1021/jm301338q] [PMID: 23316863]
[99]
Al-Horani, R.A.; Desai, U.R. Designing allosteric inhibitors of factor XIa. Lessons from the interactions of sulfated pentagalloylglucopyranosides. J. Med. Chem., 2014, 57(11), 4805-4818.
[http://dx.doi.org/10.1021/jm500311e] [PMID: 24844380]
[100]
Al-Horani, R.A.; Gailani, D.; Desai, U.R. Allosteric inhibition of factor XIa. Sulfated non-saccharide glycosaminoglycan mimetics as promising anticoagulants. Thromb. Res., 2015, 136(2), 379-387.
[http://dx.doi.org/10.1016/j.thromres.2015.04.017] [PMID: 25935648]
[101]
Karuturi, R.; Al-Horani, R.A.; Mehta, S.C.; Gailani, D.; Desai, U.R. Discovery of allosteric modulators of factor XIa by targeting hydrophobic domains adjacent to its heparin-binding site. J. Med. Chem., 2013, 56(6), 2415-2428.
[http://dx.doi.org/10.1021/jm301757v] [PMID: 23451707]
[102]
Al-Horani, R.A.; Karuturi, R.; White, D.T.; Desai, U.R. Plasmin regulation through allosteric, sulfated, small molecules. Molecules, 2015, 20(1), 608-624.
[http://dx.doi.org/10.3390/molecules20010608] [PMID: 25569517]
[103]
Afosah, D.K.; Al-Horani, R.A.; Sankaranarayanan, N.V.; Desai, U.R. Potent, selective, allosteric inhibition of human plasmin by sulfated non-saccharide glycosaminoglycan mimetics. J. Med. Chem., 2017, 60(2), 641-657.
[http://dx.doi.org/10.1021/acs.jmedchem.6b01474] [PMID: 27976897]
[104]
Luster, A.D. Chemokines--chemotactic cytokines that mediate inflammation. N. Engl. J. Med., 1998, 338(7), 436-445.
[http://dx.doi.org/10.1056/NEJM199802123380706] [PMID: 9459648]
[105]
Wells, T.N.; Power, C.A.; Proudfoot, A.E. Definition, function and pathophysiological significance of chemokine receptors. Trends Pharmacol. Sci., 1998, 19(9), 376-380.
[http://dx.doi.org/10.1016/S0165-6147(98)01247-4] [PMID: 9786026]
[106]
Rollins, B.J. Chemokines. Blood, 1997, 90(3), 909-928.
[http://dx.doi.org/10.1182/blood.V90.3.909] [PMID: 9242519]
[107]
Rossi, D.; Zlotnik, A. The biology of chemokines and their receptors. Annu. Rev. Immunol., 2000, 18, 217-242.
[http://dx.doi.org/10.1146/annurev.immunol.18.1.217] [PMID: 10837058]
[108]
Kuschert, G.S.; Coulin, F.; Power, C.A.; Proudfoot, A.E.; Hubbard, R.E.; Hoogewerf, A.J.; Wells, T.N. Glycosaminoglycans interact selectively with chemokines and modulate receptor binding and cellular responses. Biochemistry, 1999, 38(39), 12959-12968.
[http://dx.doi.org/10.1021/bi990711d] [PMID: 10504268]
[109]
Johnson, Z.; Proudfoot, A.E.; Handel, T.M. Interaction of chemokines and glycosaminoglycans: a new twist in the regulation of chemokine function with opportunities for therapeutic intervention. Cytokine Growth Factor Rev., 2005, 16(6), 625-636.
[http://dx.doi.org/10.1016/j.cytogfr.2005.04.006] [PMID: 15990353]
[110]
Asada, M.; Shinomiya, M.; Suzuki, M.; Honda, E.; Sugimoto, R.; Ikekita, M.; Imamura, T. Glycosaminoglycan affinity of the complete fibroblast growth factor family. Biochim. Biophys. Acta, 2009, 1790(1), 40-48.
[http://dx.doi.org/10.1016/j.bbagen.2008.09.001] [PMID: 18835578]
[111]
Hoogewerf, A.J.; Leone, J.W.; Reardon, I.M.; Howe, W.J.; Asa, D.; Heinrikson, R.L.; Ledbetter, S.R. CXC chemokines connective tissue activating peptide-III and neutrophil activating peptide-2 are heparin/heparan sulfate-degrading enzymes. J. Biol. Chem., 1995, 270(7), 3268-3277.
[http://dx.doi.org/10.1074/jbc.270.7.3268] [PMID: 7852412]
[112]
Witt, D.P.; Lander, A.D. Differential binding of chemokines to glycosaminoglycan subpopulations. Curr. Biol., 1994, 4(5), 394-400.
[http://dx.doi.org/10.1016/S0960-9822(00)00088-9] [PMID: 7922353]
[113]
Ornitz, D.M.; Itoh, N. Fibroblast growth factors. Genome Biol., 2001, 2(3), S3005.
[http://dx.doi.org/10.1186/gb-2001-2-3-reviews3005] [PMID: 11276432]
[114]
Shute, J. Glycosaminoglycan and chemokine/growth factor interactions. Handb. Exp. Pharmacol., 2012, (207), 307-324.
[http://dx.doi.org/10.1007/978-3-642-23056-1_13] [PMID: 22566230]
[115]
Turner, N.; Grose, R. Fibroblast growth factor signalling: from development to cancer. Nat. Rev. Cancer, 2010, 10(2), 116-129.
[http://dx.doi.org/10.1038/nrc2780] [PMID: 20094046]
[116]
Pantoliano, M.W.; Horlick, R.A.; Springer, B.A.; Van Dyk, D.E.; Tobery, T.; Wetmore, D.R.; Lear, J.D.; Nahapetian, A.T.; Bradley, J.D.; Sisk, W.P. Multivalent ligand-receptor binding interactions in the fibroblast growth factor system produce a cooperative growth factor and heparin mechanism for receptor dimerization. Biochemistry, 1994, 33(34), 10229-10248.
[http://dx.doi.org/10.1021/bi00200a003] [PMID: 7520751]
[117]
Brown, A.; Robinson, C.J.; Gallagher, J.T.; Blundell, T.L. Cooperative heparin-mediated oligomerization of fibroblast growth factor-1 (FGF1) precedes recruitment of FGFR2 to ternary complexes. Biophys. J., 2013, 104(8), 1720-1730.
[http://dx.doi.org/10.1016/j.bpj.2013.02.051] [PMID: 23601319]
[118]
Thompson, L.D.; Pantoliano, M.W.; Springer, B.A. Energetic characterization of the basic fibroblast growth factor-heparin interaction: identification of the heparin binding domain. Biochemistry, 1994, 33(13), 3831-3840.
[http://dx.doi.org/10.1021/bi00179a006] [PMID: 8142385]
[119]
WuDunn, D.; Spear, P.G. Initial interaction of herpes simplex virus with cells is binding to heparan sulfate. J. Virol., 1989, 63(1), 52-58.
[http://dx.doi.org/10.1128/JVI.63.1.52-58.1989] [PMID: 2535752]
[120]
Shukla, D.; Spear, P.G. Herpesviruses and heparan sulfate: an intimate relationship in aid of viral entry. J. Clin. Invest., 2001, 108(4), 503-510.
[http://dx.doi.org/10.1172/JCI200113799] [PMID: 11518721]
[121]
Tiwari, V.; Clement, C.; Xu, D.; Valyi-Nagy, T.; Yue, B.Y.J.T.; Liu, J.; Shukla, D. Role for 3-O-sulfated heparan sulfate as the receptor for herpes simplex virus type 1 entry into primary human corneal fibroblasts. J. Virol., 2006, 80(18), 8970-8980.
[http://dx.doi.org/10.1128/JVI.00296-06] [PMID: 16940509]
[122]
Matos, P.M.; Andreu, D.; Santos, N.C.; Gutiérrez-Gallego, R. Structural requirements of glycosaminoglycans for their interaction with HIV-1 envelope glycoprotein gp120. Arch. Virol., 2014, 159(3), 555-560.
[http://dx.doi.org/10.1007/s00705-013-1831-3] [PMID: 24046088]
[123]
Crublet, E.; Andrieu, J.P.; Vivès, R.R.; Lortat-Jacob, H. The HIV-1 envelope glycoprotein gp120 features four heparan sulfate binding domains, including the co-receptor binding site. J. Biol. Chem., 2008, 283(22), 15193-15200.
[http://dx.doi.org/10.1074/jbc.M800066200] [PMID: 18378683]
[124]
Gangji, R.N.; Sankaranarayanan, N.V.; Elste, J.; Al-Horani, R.A.; Afosah, D.K.; Joshi, R.; Tiwari, V.; Desai, U.R. Inhibition of herpes simplex virus-1 entry into human cells by non-saccharide glycosaminoglycan mimetics. ACS Med. Chem. Lett., 2018, 9(8), 797-802.
[http://dx.doi.org/10.1021/acsmedchemlett.7b00364] [PMID: 30128070]
[125]
Lima, R.T.; Seca, H.; Palmeira, A.; Fernandes, M.X.; Castro, F.; Correia-da-Silva, M.; Nascimento, M.S.; Sousa, E.; Pinto, M.; Vasconcelos, M.H. Sulfated small molecules targeting eBV in Burkitt lymphoma: from in silico screening to the evidence of in vitro effect on viral episomal DNA. Chem. Biol. Drug Des., 2013, 81(5), 631-644.
[http://dx.doi.org/10.1111/cbdd.12109] [PMID: 23350710]
[126]
Raman, R.; Sasisekharan, V.; Sasisekharan, R. Structural insights into biological roles of protein-glycosaminoglycan interactions. Chem. Biol., 2005, 12(3), 267-277.
[http://dx.doi.org/10.1016/j.chembiol.2004.11.020] [PMID: 15797210]
[127]
Pervin, A.; Gallo, C.; Jandik, K.A.; Han, X.J.; Linhardt, R.J. Preparation and structural characterization of large heparin-derived oligosaccharides. Glycobiology, 1995, 5(1), 83-95.
[http://dx.doi.org/10.1093/glycob/5.1.83] [PMID: 7772871]
[128]
Pan, J.; Qian, Y.; Zhou, X.; Pazandak, A.; Frazier, S.B.; Weiser, P.; Lu, H.; Zhang, L. Oversulfated chondroitin sulfate is not the sole contaminant in heparin. Nat. Biotechnol., 2010, 28(3), 203-207.
[http://dx.doi.org/10.1038/nbt0310-203] [PMID: 20212477]
[129]
Guerrini, M.; Beccati, D.; Shriver, Z.; Naggi, A.; Viswanathan, K.; Bisio, A.; Capila, I.; Lansing, J.C.; Guglieri, S.; Fraser, B.; Al-Hakim, A.; Gunay, N.S.; Zhang, Z.; Robinson, L.; Buhse, L.; Nasr, M.; Woodcock, J.; Langer, R.; Venkataraman, G.; Linhardt, R.J.; Casu, B.; Torri, G.; Sasisekharan, R. Oversulfated chondroitin sulfate is a contaminant in heparin associated with adverse clinical events. Nat. Biotechnol., 2008, 26(6), 669-675.
[http://dx.doi.org/10.1038/nbt1407] [PMID: 18437154]
[130]
Blossom, D.B.; Kallen, A.J.; Patel, P.R.; Elward, A.; Robinson, L.; Gao, G.; Langer, R.; Perkins, K.M.; Jaeger, J.L.; Kurkjian, K.M.; Jones, M.; Schillie, S.F.; Shehab, N.; Ketterer, D.; Venkataraman, G.; Kishimoto, T.K.; Shriver, Z.; McMahon, A.W.; Austen, K.F.; Kozlowski, S.; Srinivasan, A.; Turabelidze, G.; Gould, C.V.; Arduino, M.J.; Sasisekharan, R. Outbreak of adverse reactions associated with contaminated heparin. N. Engl. J. Med., 2008, 359(25), 2674-2684.
[http://dx.doi.org/10.1056/NEJMoa0806450] [PMID: 19052120]
[131]
Kishimoto, T.K.; Viswanathan, K.; Ganguly, T.; Elankumaran, S.; Smith, S.; Pelzer, K.; Lansing, J.C.; Sriranganathan, N.; Zhao, G.; Galcheva-Gargova, Z.; Al-Hakim, A.; Bailey, G.S.; Fraser, B.; Roy, S.; Rogers-Cotrone, T.; Buhse, L.; Whary, M.; Fox, J.; Nasr, M.; Dal Pan, G.J.; Shriver, Z.; Langer, R.S.; Venkataraman, G.; Austen, K.F.; Woodcock, J.; Sasisekharan, R. Contaminated heparin associated with adverse clinical events and activation of the contact system. N. Engl. J. Med., 2008, 358(23), 2457-2467.
[http://dx.doi.org/10.1056/NEJMoa0803200] [PMID: 18434646]
[132]
Liu, H.; Zhang, Z.; Linhardt, R.J. Lessons learned from the contamination of heparin. Nat. Prod. Rep., 2009, 26(3), 313-321.
[http://dx.doi.org/10.1039/b819896a] [PMID: 19240943]
[133]
DeAngelis, P.L. Glycosaminoglycan polysaccharide biosynthesis and production: today and tomorrow. Appl. Microbiol. Biotechnol., 2012, 94(2), 295-305.
[http://dx.doi.org/10.1007/s00253-011-3801-6] [PMID: 22391966]
[134]
Oduah, E.I.; Linhardt, R.J.; Sharfstein, S.T. Heparin: Past, present, and future. Pharmaceuticals (Basel), 2016, 9(3), 1-12.
[http://dx.doi.org/10.3390/ph9030038] [PMID: 27384570]
[135]
Ernst, B.; Magnani, J.L. From carbohydrate leads to glycomimetic drugs. Nat. Rev. Drug Discov., 2009, 8(8), 661-677.
[http://dx.doi.org/10.1038/nrd2852] [PMID: 19629075]
[136]
Magnani, J.L.; Ernst, B. Glycomimetic drugs--a new source of therapeutic opportunities. Discov. Med., 2009, 8(43), 247-252.
[PMID: 20040279]
[137]
Sankaranarayanan, N.V.; Sarkar, A.; Desai, U.R.; Mosier, P.D. Designing “high-affinity, high-specificity” glycosaminoglycan sequences through computerized modeling. Methods Mol. Biol., 2015, 1229, 289-314.
[http://dx.doi.org/10.1007/978-1-4939-1714-3_24] [PMID: 25325961]
[138]
Sankaranarayanan, N.V.; Desai, U.R. Toward a robust computational screening strategy for identifying glycosaminoglycan sequences that display high specificity for target proteins. Glycobiology, 2014, 24(12), 1323-1333.
[http://dx.doi.org/10.1093/glycob/cwu077] [PMID: 25049239]
[139]
Raghuraman, A.; Mosier, P.D.; Desai, U.R. Finding a needle in a haystack: development of a combinatorial virtual screening approach for identifying high specificity heparin/heparan sulfate sequence(s). J. Med. Chem., 2006, 49(12), 3553-3562.
[http://dx.doi.org/10.1021/jm060092o] [PMID: 16759098]
[140]
Sarkar, A.; Desai, U.R. A simple method for discovering druggable, specific glycosaminoglycan-protein systems. Elucidation of key principles from heparin/heparan sulfate-binding proteins. PLoS One, 2015, 10(10), e0141127
[http://dx.doi.org/10.1371/journal.pone.0141127] [PMID: 26488293]
[141]
Agostino, M.; Gandhi, N.S.; Mancera, R.L. Development and application of site mapping methods for the design of glycosaminoglycans. Glycobiology, 2014, 24(9), 840-851.
[http://dx.doi.org/10.1093/glycob/cwu045] [PMID: 24859723]
[142]
Mende, M.; Bednarek, C.; Wawryszyn, M.; Sauter, P.; Biskup, M.B.; Schepers, U.; Bräse, S. Chemical synthesis of glycosaminoglycans. Chem. Rev., 2016, 116(14), 8193-8255.
[http://dx.doi.org/10.1021/acs.chemrev.6b00010] [PMID: 27410264]
[143]
DeAngelis, P.L.; Liu, J.; Linhardt, R.J. Chemoenzymatic synthesis of glycosaminoglycans: re-creating, re-modeling and re-designing nature’s longest or most complex carbohydrate chains. Glycobiology, 2013, 23(7), 764-777.
[http://dx.doi.org/10.1093/glycob/cwt016] [PMID: 23481097]
[144]
Fu, L.; Suflita, M.; Linhardt, R.J. Bioengineered heparins and heparan sulfates. Adv. Drug Deliv. Rev., 2016, 97, 237-249.
[http://dx.doi.org/10.1016/j.addr.2015.11.002] [PMID: 26555370]
[145]
Samsonov, S.A.; Pisabarro, M.T. Computational analysis of interactions in structurally available protein-glycosaminoglycan complexes. Glycobiology, 2016, 26(8), 850-861.
[http://dx.doi.org/10.1093/glycob/cww055] [PMID: 27496767]
[146]
Al-Horani, R.A.; Karuturi, R.; Verespy, S., III; Desai, U.R. Synthesis of glycosaminoglycan mimetics through sulfation of polyphenols. Methods Mol. Biol., 2015, 1229, 49-67.
[http://dx.doi.org/10.1007/978-1-4939-1714-3_7] [PMID: 25325944]
[147]
Koester, D.C.; Holkenbrink, A.; Werz, D.B. Recent advances in the synthesis of carbohydrate mimetics. Synthesis, 2010, 2010(13), 3217-3242.
[http://dx.doi.org/10.1055/s-0030-1258228]
[148]
Hu, Y.P.; Lin, S.Y.; Huang, C.Y.; Zulueta, M.M.; Liu, J.Y.; Chang, W.; Hung, S.C. Synthesis of 3-O-sulfonated heparan sulfate octasaccharides that inhibit the herpes simplex virus type 1 host-cell interaction. Nat. Chem., 2011, 3(7), 557-563.
[http://dx.doi.org/10.1038/nchem.1073] [PMID: 21697878]
[149]
de Paz, J.L.; Seeberger, P.H. Deciphering the glycosaminoglycan code with the help of microarrays. Mol. Biosyst., 2008, 4(7), 707-711.
[http://dx.doi.org/10.1039/b802217h] [PMID: 18563243]
[150]
Yin, J.; Seeberger, P.H. Applications of heparin and heparan sulfate microarrays. Methods Enzymol., 2010, 478, 197-218.
[http://dx.doi.org/10.1016/S0076-6879(10)78009-5] [PMID: 20816481]
[151]
Desai, U.R. The promise of sulfated synthetic small molecules as modulators of glycosaminoglycan function. Future Med. Chem., 2013, 5(12), 1363-1366.
[http://dx.doi.org/10.4155/fmc.13.117] [PMID: 23919545]
[152]
Correia-da-Silva, M.; Sousa, E.; Pinto, M.M. Emerging sulfated flavonoids and other polyphenols as drugs: nature as an inspiration. Med. Res. Rev., 2014, 34(2), 223-279.
[http://dx.doi.org/10.1002/med.21282] [PMID: 23553315]
[153]
Shen, A. Allosteric regulation of protease activity by small molecules. Mol. Biosyst., 2010, 6(8), 1431-1443.
[http://dx.doi.org/10.1039/c003913f] [PMID: 20539873]
[154]
Merdanovic, M.; Mönig, T.; Ehrmann, M.; Kaiser, M. Diversity of allosteric regulation in proteases. ACS Chem. Biol., 2013, 8(1), 19-26.
[http://dx.doi.org/10.1021/cb3005935] [PMID: 23181429]
[155]
Hauske, P.; Ottmann, C.; Meltzer, M.; Ehrmann, M.; Kaiser, M. Allosteric regulation of proteases. ChemBioChem, 2008, 9(18), 2920-2928.
[http://dx.doi.org/10.1002/cbic.200800528] [PMID: 19021141]
[156]
Henry, B.L.; Desai, U.R. Anticoagulants: drug discovery and development in: Burger’s medicinal chemistry, (7th ed.); , 2010, pp. 365-408.
[157]
Monien, B.H.; Desai, U.R. Antithrombin activation by nonsulfated, non-polysaccharide organic polymer. J. Med. Chem., 2005, 48(4), 1269-1273.
[http://dx.doi.org/10.1021/jm0492960] [PMID: 15715496]
[158]
Monien, B.H.; Cheang, K.I.; Desai, U.R. Mechanism of poly(acrylic acid) acceleration of antithrombin inhibition of thrombin: implications for the design of novel heparin mimics. J. Med. Chem., 2005, 48(16), 5360-5368.
[http://dx.doi.org/10.1021/jm0503648] [PMID: 16078853]
[159]
Monien, B.H.; Henry, B.L.; Raghuraman, A.; Hindle, M.; Desai, U.R. Novel chemo-enzymatic oligomers of cinnamic acids as direct and indirect inhibitors of coagulation proteinases. Bioorg. Med. Chem., 2006, 14(23), 7988-7998.
[http://dx.doi.org/10.1016/j.bmc.2006.07.066] [PMID: 16914317]
[160]
Henry, B.L.; Connell, J.; Liang, A.; Krishnasamy, C.; Desai, U.R. Interaction of antithrombin with sulfated, low molecular weight lignins: opportunities for potent, selective modulation of antithrombin function. J. Biol. Chem., 2009, 284(31), 20897-20908.
[http://dx.doi.org/10.1074/jbc.M109.013359] [PMID: 19497853]
[161]
Correia-da-Silva, M.; Sousa, E.; Duarte, B.; Marques, F.; Carvalho, F.; Cunha-Ribeiro, L.M.; Pinto, M.M. Flavonoids with an oligopolysulfated moiety: a new class of anticoagulant agents. J. Med. Chem., 2011, 54(1), 95-106.
[http://dx.doi.org/10.1021/jm1013117] [PMID: 21138266]
[162]
Correia-da-Silva, M.; Sousa, E.; Duarte, B.; Marques, F.; Carvalho, F.; Cunha-Ribeiro, L.M.; Pinto, M.M. Polysulfated xanthones: multipathway development of a new generation of dual anticoagulant/antiplatelet agents. J. Med. Chem., 2011, 54(15), 5373-5384.
[http://dx.doi.org/10.1021/jm2006589] [PMID: 21732671]
[163]
Correia-da-Silva, M.; Sousa, E.; Duarte, B.; Marques, F.; Cunha-Ribeiro, L.M.; Pinto, M.M.; Pinto, M.M. Dual anticoagulant/antiplatelet persulfated small molecules. Eur. J. Med. Chem., 2011, 46(6), 2347-2358.
[http://dx.doi.org/10.1016/j.ejmech.2011.03.016] [PMID: 21450376]
[164]
Versteeg, H.H.; Heemskerk, J.W.; Levi, M.; Reitsma, P.H. New fundamentals in hemostasis. Physiol. Rev., 2013, 93(1), 327-358.
[http://dx.doi.org/10.1152/physrev.00016.2011] [PMID: 23303912]
[165]
von dem Borne, P.A.; Meijers, J.C.; Bouma, B.N. Feedback activation of factor XI by thrombin in plasma results in additional formation of thrombin that protects fibrin clots from fibrinolysis. Blood, 1995, 86(8), 3035-3042.
[http://dx.doi.org/10.1182/blood.V86.8.3035.3035] [PMID: 7579397]
[166]
De Candia, E.; Hall, S.W.; Rutella, S.; Landolfi, R.; Andrews, R.K.; De Cristofaro, R. Binding of thrombin to glycoprotein Ib accelerates the hydrolysis of Par-1 on intact platelets. J. Biol. Chem., 2001, 276(7), 4692-4698.
[http://dx.doi.org/10.1074/jbc.M008160200] [PMID: 11084032]
[167]
Esmon, C.T. The roles of protein C and thrombomodulin in the regulation of blood coagulation. J. Biol. Chem., 1989, 264(9), 4743-4746.
[PMID: 2538457]
[168]
Henry, B.L.; Monien, B.H.; Bock, P.E.; Desai, U.R. A novel allosteric pathway of thrombin inhibition: Exosite II mediated potent inhibition of thrombin by chemo-enzymatic, sulfated dehydropolymers of 4-hydroxycinnamic acids. J. Biol. Chem., 2007, 282(44), 31891-31899.
[http://dx.doi.org/10.1074/jbc.M704257200] [PMID: 17804413]
[169]
Abdel Aziz, M.H.; Mosier, P.D.; Desai, U.R. Identification of the site of binding of sulfated, low molecular weight lignins on thrombin. Biochem. Biophys. Res. Commun., 2011, 413(2), 348-352.
[http://dx.doi.org/10.1016/j.bbrc.2011.08.102] [PMID: 21893043]
[170]
Mehta, A.Y.; Thakkar, J.N.; Mohammed, B.M.; Martin, E.J.; Brophy, D.F.; Kishimoto, T.; Desai, U.R. Targeting the GPIbα binding site of thrombin to simultaneously induce dual anticoagulant and antiplatelet effects. J. Med. Chem., 2014, 57(7), 3030-3039.
[http://dx.doi.org/10.1021/jm4020026] [PMID: 24635452]
[171]
Mehta, A.Y.; Desai, U.R. Substantial non-electrostatic forces are needed to induce allosteric disruption of thrombin’s active site through exosite 2. Biochem. Biophys. Res. Commun., 2014, 452(3), 813-816.
[http://dx.doi.org/10.1016/j.bbrc.2014.09.003] [PMID: 25201728]
[172]
Mehta, A.Y.; Mohammed, B.M.; Martin, E.J.; Brophy, D.F.; Gailani, D.; Desai, U.R. Allosterism-based simultaneous, dual anticoagulant and antiplatelet action: allosteric inhibitor targeting the glycoprotein Ibα-binding and heparin-binding site of thrombin. J. Thromb. Haemost., 2016, 14(4), 828-838.
[http://dx.doi.org/10.1111/jth.13254] [PMID: 26748875]
[173]
Nahain, A.A.; Ignjatovic, V.; Monagle, P.; Tsanaktsidis, J.; Ferro, V. Heparin mimetics with anticoagulant activity. Med. Res. Rev., 2018, 38(5), 1582-1613.
[http://dx.doi.org/10.1002/med.21489] [PMID: 29446104]
[174]
Al-Horani, R.A.; Desai, U.R. Factor XIa inhibitors: A review of the patent literature. Expert Opin. Ther. Pat., 2016, 26(3), 323-345.
[http://dx.doi.org/10.1517/13543776.2016.1154045] [PMID: 26881476]
[175]
He, R.; Chen, D.; He, S. Factor XI: hemostasis, thrombosis, and antithrombosis. Thromb. Res., 2012, 129(5), 541-550.
[http://dx.doi.org/10.1016/j.thromres.2011.11.051] [PMID: 22197449]
[176]
Emsley, J.; McEwan, P.A.; Gailani, D. Structure and function of factor XI. Blood, 2010, 115(13), 2569-2577.
[http://dx.doi.org/10.1182/blood-2009-09-199182] [PMID: 20110423]
[177]
Gailani, D.; Smith, S.B. Structural and functional features of factor XI. J. Thromb. Haemost., 2009, 7(Suppl. 1), 75-78.
[http://dx.doi.org/10.1111/j.1538-7836.2009.03414.x] [PMID: 19630773]
[178]
Smith, G.F.; Sundboom, J.L. Heparin and protease inhibition. II. The role of heparin in the ATIII inactivation of thrombin, plasmin, and trypsin. Thromb. Res., 1981, 22(1-2), 115-133.
[http://dx.doi.org/10.1016/0049-3848(81)90314-5] [PMID: 6457414]
[179]
Rosenberg, R.D. The effect of heparin on factor XIa and plasmin. Thromb. Diath. Haemorrh., 1975, 33(1), 51-62.
[http://dx.doi.org/10.1055/s-0038-1647810] [PMID: 235160]
[180]
Yomtova, V.M.; Stambolieva, N.A.; Blagoev, B.M. Kinetic study of the effect of heparin on the amidase activity of trypsin, plasmin and urokinase. Thromb. Haemost., 1983, 49(3), 199-203.
[http://dx.doi.org/10.1055/s-0038-1657362] [PMID: 6224310]
[181]
Machovich, R.; Bauer, P.I.; Arányi, P.; Kecskés, E.; Büki, K.G.; Horváth, I. Kinetic analysis of the heparin-enhanced plasmin--antithrombin III reaction. Apparent catalytic role of heparin. Biochem. J., 1981, 199(3), 521-526.
[http://dx.doi.org/10.1042/bj1990521] [PMID: 6462134]
[182]
Henry, B.L.; Abdel Aziz, M.; Zhou, Q.; Desai, U.R. Sulfated, low-molecular-weight lignins are potent inhibitorsof plasmin, in addition to thrombin and factor Xa: Novel opportunity for controlling complex pathologies. Thromb. Haemost., 2010, 103(3), 507-515.
[http://dx.doi.org/10.1160/TH09-07-0454] [PMID: 20024500]
[183]
Al-Horani, R.A.; Karuturi, R.; Lee, M.; Afosah, D.K.; Desai, U.R. Allosteric inhibition of factor XIIIa. Non-saccharide glycosaminoglycan mimetics, but not glycosaminoglycans, exhibit promising inhibition profile. PLoS One, 2016, 11(7), e0160189
[http://dx.doi.org/10.1371/journal.pone.0160189] [PMID: 27467511]
[184]
Aleman, M.M.; Byrnes, J.R.; Wang, J.G.; Tran, R.; Lam, W.A.; Di Paola, J.; Mackman, N.; Degen, J.L.; Flick, M.J.; Wolberg, A.S. Factor XIII activity mediates red blood cell retention in venous thrombi. J. Clin. Invest., 2014, 124(8), 3590-3600.
[http://dx.doi.org/10.1172/JCI75386] [PMID: 24983320]
[185]
Byrnes, J.R.; Duval, C.; Wang, Y.; Hansen, C.E.; Ahn, B.; Mooberry, M.J.; Clark, M.A.; Johnsen, J.M.; Lord, S.T.; Lam, W.A.; Meijers, J.C.; Ni, H.; Ariëns, R.A.; Wolberg, A.S. Factor XIIIa-dependent retention of red blood cells in clots is mediated by fibrin α-chain crosslinking. Blood, 2015, 126(16), 1940-1948.
[http://dx.doi.org/10.1182/blood-2015-06-652263] [PMID: 26324704]
[186]
Flick, M.J.; Du, X.; Witte, D.P.; Jirousková, M.; Soloviev, D.A.; Busuttil, S.J.; Plow, E.F.; Degen, J.L. Leukocyte engagement of fibrin(ogen) via the integrin receptor alphaMbeta2/Mac-1 is critical for host inflammatory response in vivo. J. Clin. Invest., 2004, 113(11), 1596-1606.
[http://dx.doi.org/10.1172/JCI20741] [PMID: 15173886]
[187]
Lauer, P.; Metzner, H.J.; Zettlmeissl, G.; Li, M.; Smith, A.G.; Lathe, R.; Dickneite, G. Targeted inactivation of the mouse locus encoding coagulation factor XIII-A: hemostatic abnormalities in mutant mice and characterization of the coagulation deficit. Thromb. Haemost., 2002, 88(6), 967-974.
[http://dx.doi.org/10.1055/s-0037-1613342] [PMID: 12529747]
[188]
Raman, K.; Karuturi, R.; Swarup, V.P.; Desai, U.R.; Kuberan, B. Discovery of novel sulfonated small molecules that inhibit vascular tube formation. Bioorg. Med. Chem. Lett., 2012, 22(13), 4467-4470.
[http://dx.doi.org/10.1016/j.bmcl.2012.04.014] [PMID: 22627041]
[189]
Belting, M. Glycosaminoglycans in cancer treatment. Thromb. Res., 2014, 133(Suppl. 2), S95-S101.
[http://dx.doi.org/10.1016/S0049-3848(14)50016-3] [PMID: 24862153]
[190]
Patel, N.J.; Karuturi, R.; Al-Horani, R.A.; Baranwal, S.; Patel, J.; Desai, U.R.; Patel, B.B. Synthetic, non-saccharide, glycosaminoglycan mimetics selectively target colon cancer stem cells. ACS Chem. Biol., 2014, 9(8), 1826-1833.
[http://dx.doi.org/10.1021/cb500402f] [PMID: 24968014]
[191]
Boothello, R.S.; Patel, N.J.; Sharon, C.; Abdelfadiel, E.I.; Morla, S.; Brophy, D.F.; Lippman, H.R.; Desai, U.R.; Patel, B.B. A unique non-saccharide mimetic of heparin hexasaccharide inhibits colon cancer stem cells via p38 MAP kinase activation. Mol. Cancer Ther., 2019, 18(1), 51-61.
[http://dx.doi.org/10.1158/1535-7163.MCT-18-0104] [PMID: 30337351]
[192]
Nagarajan, B.; Sankaranarayanan, N.V.; Patel, B.B.; Desai, U.R. A molecular dynamics-based algorithm for evaluating the glycosaminoglycan mimicking potential of synthetic, homogenous, sulfated small molecules. PLoS One, 2017, 12(2), e0171619
[http://dx.doi.org/10.1371/journal.pone.0171619] [PMID: 28182755]
[193]
Patel, N.J.; Sharon, C.; Baranwal, S.; Boothello, R.S.; Desai, U.R.; Patel, B.B. Heparan sulfate hexasaccharide selectively inhibits cancer stem cells self-renewal by activating p38 MAP kinase. Oncotarget, 2016, 7(51), 84608-84622.
[http://dx.doi.org/10.18632/oncotarget.12358] [PMID: 27705927]
[194]
Saluja, B.; Thakkar, J.N.; Li, H.; Desai, U.R.; Sakagami, M. Novel low molecular weight lignins as potential anti-emphysema agents: In vitro triple inhibitory activity against elastase, oxidation and inflammation. Pulm. Pharmacol. Ther., 2013, 26(2), 296-304.
[http://dx.doi.org/10.1016/j.pupt.2012.12.009] [PMID: 23280431]
[195]
Saluja, B.; Li, H.; Desai, U.R.; Voelkel, N.F.; Sakagami, M. Sulfated caffeic acid dehydropolymer attenuates elastase and cigarette smoke extract-induced emphysema in rats: sustained activity and a need of pulmonary delivery. Lung, 2014, 192(4), 481-492.
[http://dx.doi.org/10.1007/s00408-014-9597-2] [PMID: 24831783]
[196]
Truong, T.M.; Li, H.; Dhapare, S.; Desai, U.R.; Voelkel, N.F.; Sakagami, M. Sulfated dehydropolymer of caffeic acid: In vitro anti-lung cell death activity and in vivo intervention in emphysema induced by VEGF receptor blockade. Pulm. Pharmacol. Ther., 2017, 45, 181-190.
[http://dx.doi.org/10.1016/j.pupt.2017.06.007] [PMID: 28648907]
[197]
Rees, C.R.; Costin, J.M.; Fink, R.C.; McMichael, M.; Fontaine, K.A.; Isern, S.; Michael, S.F. In vitro inhibition of dengue virus entry by p-sulfoxy-cinnamic acid and structurally related combinatorial chemistries. Antiviral Res., 2008, 80(2), 135-142.
[http://dx.doi.org/10.1016/j.antiviral.2008.05.007] [PMID: 18606464]
[198]
Vilas-Boas, C.; Sousa, E.; Pinto, M.; Correia-da-Silva, M. An antifouling model from the sea: a review of 25 years of zosteric acid studies. Biofouling, 2017, 33(10), 927-942.
[http://dx.doi.org/10.1080/08927014.2017.1391951] [PMID: 29171304]
[199]
Almeida, J.R.; Correia-da-Silva, M.; Sousa, E.; Antunes, J.; Pinto, M.; Vasconcelos, V.; Cunha, I. Antifouling potential of Nature-inspired sulfated compounds. Sci. Rep., 2017, 7, 42424.
[http://dx.doi.org/10.1038/srep42424] [PMID: 28205590]
[200]
Severin, I.C.; Soares, A.; Hantson, J.; Teixeira, M.; Sachs, D.; Valognes, D.; Scheer, A.; Schwarz, M.K.; Wells, T.N.; Proudfoot, A.E.; Shaw, J. Glycosaminoglycan analogs as a novel anti-inflammatory strategy. Front. Immunol., 2012, 3, 293.
[http://dx.doi.org/10.3389/fimmu.2012.00293] [PMID: 23087686]
[201]
Mathias, D.K.; Pastrana-Mena, R.; Ranucci, E.; Tao, D.; Ferruti, P.; Ortega, C.; Staples, G.O.; Zaia, J.; Takashima, E.; Tsuboi, T.; Borg, N.A.; Verotta, L.; Dinglasan, R.R. A small molecule glycosaminoglycan mimetic blocks Plasmodium invasion of the mosquito midgut. PLoS Pathog., 2013, 9(11), e1003757
[http://dx.doi.org/10.1371/journal.ppat.1003757] [PMID: 24278017]
[202]
Al-Horani, R.A.; Desai, U.R. Chemical sulfation of small molecules - advances and challenges. Tetrahedron, 2010, 66(16), 2907-2918.
[http://dx.doi.org/10.1016/j.tet.2010.02.015] [PMID: 20689724]
[203]
Liang, W.G.; Triandafillou, C.G.; Huang, T.Y.; Zulueta, M.M.; Banerjee, S.; Dinner, A.R.; Hung, S.C.; Tang, W.J. Structural basis for oligomerization and glycosaminoglycan binding of CCL5 and CCL3. Proc. Natl. Acad. Sci. USA, 2016, 113(18), 5000-5005.
[http://dx.doi.org/10.1073/pnas.1523981113] [PMID: 27091995]
[204]
Wu, L.; Viola, C.M.; Brzozowski, A.M.; Davies, G.J. Corrigendum: Structural characterization of human heparanase reveals insights into substrate recognition. Nat. Struct. Mol. Biol., 2016, 23(1), 91.
[http://dx.doi.org/10.1038/nsmb0116-91] [PMID: 26733221]
[205]
Dasgupta, J.; Bienkowska-Haba, M.; Ortega, M.E.; Patel, H.D.; Bodevin, S.; Spillmann, D.; Bishop, B.; Sapp, M.; Chen, X.S. Structural basis of oligosaccharide receptor recognition by human papillomavirus. J. Biol. Chem., 2011, 286(4), 2617-2624.
[http://dx.doi.org/10.1074/jbc.M110.160184] [PMID: 21115492]
[206]
Johnson, D.J.; Langdown, J.; Huntington, J.A. Molecular basis of factor IXa recognition by heparin-activated antithrombin revealed by a 1.7-A structure of the ternary complex. Proc. Natl. Acad. Sci. USA, 2010, 107(2), 645-650.
[http://dx.doi.org/10.1073/pnas.0910144107] [PMID: 20080729]
[207]
Pellegrini, L.; Burke, D.F.; von Delft, F.; Mulloy, B.; Blundell, T.L. Crystal structure of fibroblast growth factor receptor ectodomain bound to ligand and heparin. Nature, 2000, 407(6807), 1029-1034.
[http://dx.doi.org/10.1038/35039551] [PMID: 11069186]
[208]
Schlessinger, J.; Plotnikov, A.N.; Ibrahimi, O.A.; Eliseenkova, A.V.; Yeh, B.K.; Yayon, A.; Linhardt, R.J.; Mohammadi, M. Crystal structure of a ternary FGF-FGFR-heparin complex reveals a dual role for heparin in FGFR binding and dimerization. Mol. Cell, 2000, 6(3), 743-750.
[http://dx.doi.org/10.1016/S1097-2765(00)00073-3] [PMID: 11030354]
[209]
Khatun, Z.; Nurunnabi, M.; Cho, K.J.; Lee, Y-K. Imaging of the GI tract by QDs loaded heparin-deoxycholic acid (DOCA) nanoparticles. Carbohydr. Polym., 2012, 90(4), 1461-1468.
[http://dx.doi.org/10.1016/j.carbpol.2012.07.016] [PMID: 22944403]
[210]
Kim, S.K.; Lee, D.Y.; Kim, C.Y.; Nam, J.H.; Moon, H.T.; Byun, Y. A newly developed oral heparin derivative for deep vein thrombosis: non-human primate study. J. Control. Release, 2007, 123(2), 155-163.
[http://dx.doi.org/10.1016/j.jconrel.2007.08.007] [PMID: 17884230]
[211]
Kim, S.K.; Vaishali, B.; Lee, E.; Lee, S.; Lee, Y-K.; Kumar, T.S.; Moon, H.T.; Byun, Y. Oral delivery of chemical conjugates of heparin and deoxycholic acid in aqueous formulation. Thromb. Res., 2006, 117(4), 419-427.
[http://dx.doi.org/10.1016/j.thromres.2005.03.027] [PMID: 15913716]
[212]
Lee, Y.; Kim, S.H.; Byun, Y. Oral delivery of new heparin derivatives in rats. Pharm. Res., 2000, 17(10), 1259-1264.
[http://dx.doi.org/10.1023/A:1026474919869] [PMID: 11145232]
[213]
Motlekar, N.A.; Srivenugopal, K.S.; Wachtel, M.S.; Youan, B.B. Modulation of gastrointestinal permeability of low-molecular-weight heparin by L-arginine: in-vivo and in-vitro evaluation. J. Pharm. Pharmacol., 2006, 58(5), 591-598.
[http://dx.doi.org/10.1211/jpp.58.5.0003] [PMID: 16640827]
[214]
Motlekar, N.A.; Srivenugopal, K.S.; Wachtel, M.S.; Youan, B.B.C. Evaluation of the oral bioavailability of low molecular weight heparin formulated with glycyrrhetinic acid as permeation enhancer. Drug Dev. Res., 2006, 67(2), 166-174.
[http://dx.doi.org/10.1002/ddr.20087] [PMID: 17710191]
[215]
Neves, A.R.; Correia-da-Silva, M.; Sousa, E.; Pinto, M. Strategies to overcome heparins’ low oral bioavailability. Pharmaceuticals (Basel), 2016, 9(3), E37
[http://dx.doi.org/10.3390/ph9030037] [PMID: 27367704]
[216]
Plosker, G.L. Acamprosate: A review of its use in alcohol dependence. Drugs, 2015, 75(11), 1255-1268.
[http://dx.doi.org/10.1007/s40265-015-0423-9] [PMID: 26084940]
[217]
Abushakra, S.; Porsteinsson, A.; Scheltens, P.; Sadowsky, C.; Vellas, B.; Cummings, J.; Gauthier, S.; Hey, J.A.; Power, A.; Wang, P.; Shen, L.; Tolar, M. Clinical effects of tramiprosate in APOE4/4 homozygous patients with mild alzheimer’s disease suggest disease modification potential. J. Prev. Alzheimers Dis., 2017, 4(3), 149-156.
[PMID: 29182706]
[218]
Rumjon, A.; Coats, T.; Javaid, M.M. Review of eprodisate for the treatment of renal disease in AA amyloidosis. Int. J. Nephrol. Renovasc. Dis., 2012, 5, 37-43.
[http://dx.doi.org/10.2147/IJNRD.S19165] [PMID: 22427728]
[219]
Abdeen, S.; Salim, N.; Mammadova, N.; Summers, C.M.; Goldsmith-Pestana, K.; McMahon-Pratt, D.; Schultz, P.G.; Horwich, A.L.; Chapman, E.; Johnson, S.M. Targeting the HSP60/10 chaperonin systems of Trypanosoma brucei as a strategy for treating African sleeping sickness. Bioorg. Med. Chem. Lett., 2016, 26(21), 5247-5253.
[http://dx.doi.org/10.1016/j.bmcl.2016.09.051] [PMID: 27720295]
[220]
Rondanin, R.; Fochi, S.; Baruchello, R.; Bernardi, T.; Oliva, P.; Semeraro, F.; Simoni, D.; Giannini, G. Arylamidonaphtalene sulfonate compounds as a novel class of heparanase inhibitors. Bioorg. Med. Chem. Lett., 2017, 27(18), 4421-4425.
[http://dx.doi.org/10.1016/j.bmcl.2017.08.013] [PMID: 28811133]
[221]
Ferla, S.; Netzler, N.E.; Ferla, S.; Veronese, S.; Tuipulotu, D.E.; Guccione, S.; Brancale, A.; White, P.A.; Bassetto, M. In silico screening for human norovirus antivirals reveals a novel non-nucleoside inhibitor of the viral polymerase. Sci. Rep., 2018, 8(1), 4129.
[http://dx.doi.org/10.1038/s41598-018-22303-y] [PMID: 29515206]
[222]
Naviaux, R.K.; Curtis, B.; Li, K.; Naviaux, J.C.; Bright, A.T.; Reiner, G.E.; Westerfield, M.; Goh, S.; Alaynick, W.A.; Wang, L.; Capparelli, E.V.; Adams, C.; Sun, J.; Jain, S.; He, F.; Arellano, D.A.; Mash, L.E.; Chukoskie, L.; Lincoln, A.; Townsend, J. Low-dose suramin in autism spectrum disorder: a small, phase I/II, randomized clinical trial. Ann. Clin. Transl. Neurol., 2017, 4(7), 491-505.
[http://dx.doi.org/10.1002/acn3.424] [PMID: 28695149]
[223]
Gustafsen, C.; Olsen, D.; Vilstrup, J.; Lund, S.; Reinhardt, A.; Wellner, N.; Larsen, T.; Andersen, C.B.F.; Weyer, K.; Li, J.P.; Seeberger, P.H.; Thirup, S.; Madsen, P.; Glerup, S. Heparan sulfate proteoglycans present PCSK9 to the LDL receptor. Nat. Commun., 2017, 8(1), 503.
[http://dx.doi.org/10.1038/s41467-017-00568-7] [PMID: 28894089]
[224]
Frommherz, K.J.; Faller, B.; Bieth, J.G. Heparin strongly decreases the rate of inhibition of neutrophil elastase by alpha 1-proteinase inhibitor. J. Biol. Chem., 1991, 266(23), 15356-15362.
[PMID: 1869557]
[225]
Jordan, R.E.; Oosta, G.M.; Gardner, W.T.; Rosenberg, R.D. The binding of low molecular weight heparin to hemostatic enzymes. J. Biol. Chem., 1980, 255(21), 10073-10080.
[PMID: 6448845]
[226]
Krieger, E.; Geretti, E.; Brandner, B.; Goger, B.; Wells, T.N.; Kungl, A.J. A structural and dynamic model for the interaction of interleukin-8 and glycosaminoglycans: support from isothermal fluorescence titrations. Proteins, 2004, 54(4), 768-775.
[http://dx.doi.org/10.1002/prot.10590] [PMID: 14997572]
[227]
Mayo, K.H.; Ilyina, E.; Roongta, V.; Dundas, M.; Joseph, J.; Lai, C.K.; Maione, T.; Daly, T.J. Heparin binding to platelet factor-4. An NMR and site-directed mutagenesis study: arginine residues are crucial for binding. Biochem. J., 1995, 312(Pt 2), 357-365.
[http://dx.doi.org/10.1042/bj3120357] [PMID: 8526843]
[228]
Loscalzo, J.; Melnick, B.; Handin, R.I. The interaction of platelet factor four and glycosaminoglycans. Arch. Biochem. Biophys., 1985, 240(1), 446-455.
[http://dx.doi.org/10.1016/0003-9861(85)90049-9] [PMID: 2409923]
[229]
Shukla, D.; Liu, J.; Blaiklock, P.; Shworak, N.W.; Bai, X.; Esko, J.D.; Cohen, G.H.; Eisenberg, R.J.; Rosenberg, R.D.; Spear, P.G. A novel role for 3-O-sulfated heparan sulfate in herpes simplex virus 1 entry. Cell, 1999, 99(1), 13-22.
[http://dx.doi.org/10.1016/S0092-8674(00)80058-6] [PMID: 10520990]
[230]
Liu, J.; Shriver, Z.; Pope, R.M.; Thorp, S.C.; Duncan, M.B.; Copeland, R.J.; Raska, C.S.; Yoshida, K.; Eisenberg, R.J.; Cohen, G.; Linhardt, R.J.; Sasisekharan, R. Characterization of a heparan sulfate octasaccharide that binds to herpes simplex virus type 1 glycoprotein D. J. Biol. Chem., 2002, 277(36), 33456-33467.
[http://dx.doi.org/10.1074/jbc.M202034200] [PMID: 12080045]
[231]
Moulard, M.; Lortat-Jacob, H.; Mondor, I.; Roca, G.; Wyatt, R.; Sodroski, J.; Zhao, L.; Olson, W.; Kwong, P.D.; Sattentau, Q.J. Selective interactions of polyanions with basic surfaces on human immunodeficiency virus type 1 gp120. J. Virol., 2000, 74(4), 1948-1960.
[http://dx.doi.org/10.1128/JVI.74.4.1948-1960.2000] [PMID: 10644368]

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