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Current Medicinal Chemistry

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ISSN (Online): 1875-533X

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Review Article

Structural Basis of Drug Recognition by Human Serum Albumin

Author(s): Loris Leboffe, Alessandra di Masi*, Fabio Polticelli, Viviana Trezza and Paolo Ascenzi

Volume 27, Issue 30, 2020

Page: [4907 - 4931] Pages: 25

DOI: 10.2174/0929867326666190320105316

Price: $65

Abstract

Background: Human serum albumin (HSA), the most abundant protein in plasma, is a monomeric multi-domain macromolecule with at least nine binding sites for endogenous and exogenous ligands. HSA displays an extraordinary ligand binding capacity as a depot and carrier for many compounds including most acidic drugs. Consequently, HSA has the potential to influence the pharmacokinetics and pharmacodynamics of drugs.

Objective: In this review, the structural determinants of drug binding to the multiple sites of HSA are analyzed and discussed in detail. Moreover, insight into the allosteric and competitive mechanisms underpinning drug recognition, delivery, and efficacy are analyzed and discussed.

Conclusion: As several factors can modulate drug binding to HSA (e.g., concurrent administration of drugs competing for the same binding site, ligand binding to allosteric-coupled clefts, genetic inherited diseases, and post-translational modifications), ligand binding to HSA is relevant not only under physiological conditions, but also in the pharmacological therapy management.

Keywords: Human serum albumin, drug carrier, drug recognition, structural basis, allosteric modulation of drug binding, competitive modulation of drug binding.

« Previous Next »
[1]
Goodman, L.S.; Brunton, L.L.; Chabner, B.; Knollmann, B.C. Goodman & Gilman’s Pharmacological Basis of Therapeutics; McGraw-Hill: New York, 2011.
[2]
di Masi, A.; Trezza, V.; Leboffe, L.; Ascenzi, P. Human plasma lipocalins and serum albumin: plasma alternative carriers? J. Control. Release, 2016, 228, 191-205.
[http://dx.doi.org/10.1016/j.jconrel.2016.02.049] [PMID: 26951925]
[3]
Lindup, W.E.; Orme, M.C. Clinical pharmacology: plasma protein binding of drugs. Br. Med. J. (Clin. Res. Ed.), 1981, 282(6259), 212-214.
[http://dx.doi.org/10.1136/bmj.282.6259.212] [PMID: 6779954]
[4]
Schmidt, S.; Gonzalez, D.; Derendorf, H. Significance of protein binding in pharmacokinetics and pharmacodynamics. J. Pharm. Sci., 2010, 99(3), 1107-1122.
[http://dx.doi.org/10.1002/jps.21916] [PMID: 19852037]
[5]
Ascenzi, P.; Fanali, G.; Fasano, M.; Pallottini, V.; Trezza, V. Clinical relevance of drug binding to plasma proteins. J. Mol. Struct., 2014, 1077, 4-13.
[http://dx.doi.org/10.1016/j.molstruc.2013.09.053]
[6]
D’Arcy, P.F.; McElnay, J.C. Drug interactions involving the displacement of drugs from plasma protein and tissue binding sites. Pharmacol. Ther., 1982, 17(2), 211-220.
[http://dx.doi.org/10.1016/0163-7258(82)90012-2] [PMID: 6757977]
[7]
Fanali, G.; di Masi, A.; Trezza, V.; Marino, M.; Fasano, M.; Ascenzi, P. Human serum albumin: from bench to bedside. Mol. Aspects Med., 2012, 33(3), 209-290.
[http://dx.doi.org/10.1016/j.mam.2011.12.002] [PMID: 22230555]
[8]
Rimac, H.; Debeljak, Ž.; Bojić, M.; Miller, L. Displacement of drugs from human serum albumin: from molecular interactions to clinical significance. Curr. Med. Chem., 2017, 24(18), 1930-1947.
[http://dx.doi.org/10.2174/0929867324666170202152134] [PMID: 28155602]
[9]
Ghuman, J.; Zunszain, P.A.; Petitpas, I.; Bhattacharya, A.A.; Otagiri, M.; Curry, S. Structural basis of the drug-binding specificity of human serum albumin. J. Mol. Biol., 2005, 353(1), 38-52.
[http://dx.doi.org/10.1016/j.jmb.2005.07.075] [PMID: 16169013]
[10]
Wang, Z.M.; Ho, J.X.; Ruble, J.R.; Rose, J.; Rüker, F.; Ellenburg, M.; Murphy, R.; Click, J.; Soistman, E.; Wilkerson, L.; Carter, D.C. Structural studies of several clinically important oncology drugs in complex with human serum albumin. Biochim. Biophys. Acta, 2013, 1830(12), 5356-5374.
[http://dx.doi.org/10.1016/j.bbagen.2013.06.032] [PMID: 23838380]
[11]
Ferraro, G.; Massai, L.; Messori, L.; Merlino, A. Cisplatin binding to human serum albumin: a structural study. Chem. Commun. (Camb.), 2015, 51(46), 9436-9439.
[http://dx.doi.org/10.1039/C5CC01751C] [PMID: 25873085]
[12]
Zhang, Y.; Lee, P.; Liang, S.; Zhou, Z.; Wu, X.; Yang, F.; Liang, H. Structural basis of non-steroidal anti-inflammatory drug diclofenac binding to human serum albumin. Chem. Biol. Drug Des., 2015, 86(5), 1178-1184.
[http://dx.doi.org/10.1111/cbdd.12583] [PMID: 25958880]
[13]
Sakurama, K.; Kawai, A.; Tuan Giam Chuang, V.; Kanamori, Y.; Osa, M.; Taguchi, K.; Seo, H.; Maruyama, T.; Imoto, S.; Yamasaki, K.; Otagiri, M. Analysis of the binding of aripiprazole to human serum albumin: the importance of a chloro-group in the chemical structure. ACS Omega, 2018, 3(10), 13790-13797.
[http://dx.doi.org/10.1021/acsomega.8b02057] [PMID: 30411049]
[14]
Kawai, A.; Yamasaki, K.; Enokida, T.; Miyamoto, S.; Otagiri, M. Crystal structure analysis of human serum albumin complexed with sodium 4-phenylbutyrate. Biochem. Biophys. Rep., 2018, 13, 78-82.
[http://dx.doi.org/10.1016/j.bbrep.2018.01.006] [PMID: 29387812]
[15]
He, X.M.; Carter, D.C. Atomic structure and chemistry of human serum albumin. Nature, 1992, 358(6383), 209-215.
[http://dx.doi.org/10.1038/358209a0] [PMID: 1630489]
[16]
Curry, S.; Mandelkow, H.; Brick, P.; Franks, N. Crystal structure of human serum albumin complexed with fatty acid reveals an asymmetric distribution of binding sites. Nat. Struct. Biol., 1998, 5(9), 827-835.
[http://dx.doi.org/10.1038/1869] [PMID: 9731778]
[17]
Sugio, S.; Kashima, A.; Mochizuki, S.; Noda, M.; Kobayashi, K. Crystal structure of human serum albumin at 2.5 a resolution. Protein Eng., 1999, 12(6), 439-446.
[http://dx.doi.org/10.1093/protein/12.6.439] [PMID: 10388840]
[18]
Curry, S. Beyond expansion: structural studies on the transport roles of human serum albumin. Vox Sang., 2002, 83(Suppl. 1), 315-319.
[http://dx.doi.org/10.1111/j.1423-0410.2002.tb05326.x] [PMID: 12617161]
[19]
Fasano, M.; Curry, S.; Terreno, E.; Galliano, M.; Fanali, G.; Narciso, P.; Notari, S.; Ascenzi, P. The extraordinary ligand binding properties of human serum albumin. IUBMB Life, 2005, 57(12), 787-796.
[http://dx.doi.org/10.1080/15216540500404093] [PMID: 16393781]
[20]
Curry, S. Lessons from the crystallographic analysis of small molecule binding to human serum albumin. Drug Metab. Pharmacokinet., 2009, 24(4), 342-357.
[http://dx.doi.org/10.2133/dmpk.24.342] [PMID: 19745561]
[21]
Ascenzi, P.; Fasano, M. Allostery in a monomeric protein: the case of human serum albumin. Biophys. Chem., 2010, 148(1-3), 16-22.
[http://dx.doi.org/10.1016/j.bpc.2010.03.001] [PMID: 20346571]
[22]
Varshney, A.; Sen, P.; Ahmad, E.; Rehan, M.; Subbarao, N.; Khan, R.H. Ligand binding strategies of human serum albumin: how can the cargo be utilized? Chirality, 2010, 22(1), 77-87.
[http://dx.doi.org/10.1002/chir.20709] [PMID: 19319989]
[23]
Peters, T., Jr, Ed.; All about Albumin: Biochemistry, Genetics and Medical Applications; Academic Press: San Diego, London, 1996.
[24]
Mao, H.; Hajduk, P.J.; Craig, R.; Bell, R.; Borre, T.; Fesik, S.W. Rational design of diflunisal analogues with reduced affinity for human serum albumin. J. Am. Chem. Soc., 2001, 123(43), 10429-10435.
[http://dx.doi.org/10.1021/ja015955b] [PMID: 11673972]
[25]
Hein, K.L.; Kragh-Hansen, U.; Morth, J.P.; Jeppesen, M.D.; Otzen, D.; Møller, J.V.; Nissen, P. Crystallographic analysis reveals a unique lidocaine binding site on human serum albumin. J. Struct. Biol., 2010, 171(3), 353-360.
[http://dx.doi.org/10.1016/j.jsb.2010.03.014] [PMID: 20347991]
[26]
Vallianatou, T.; Lambrinidis, G.; Tsantili-Kakoulidou, A. In silico prediction of human serum albumin binding for drug leads. Expert Opin. Drug Discov., 2013, 8(5), 583-595.
[http://dx.doi.org/10.1517/17460441.2013.777424] [PMID: 23461733]
[27]
Yang, F.; Zhang, Y.; Liang, H. Interactive association of drugs binding to human serum albumin. Int. J. Mol. Sci., 2014, 15(3), 3580-3595.
[http://dx.doi.org/10.3390/ijms15033580] [PMID: 24583848]
[28]
Zsila, F. Circular dichroism spectroscopic detection of ligand binding induced subdomain IB specific structural adjustment of human serum albumin. J. Phys. Chem. B, 2013, 117(37), 10798-10806.
[http://dx.doi.org/10.1021/jp4067108] [PMID: 24004247]
[29]
Zsila, F. Subdomain IB is the third major drug binding region of human serum albumin: toward the three-sites model. Mol. Pharm., 2013, 10(5), 1668-1682.
[http://dx.doi.org/10.1021/mp400027q] [PMID: 23473402]
[30]
Bhattacharya, A.A.; Grüne, T.; Curry, S. Crystallographic analysis reveals common modes of binding of medium and long-chain fatty acids to human serum albumin. J. Mol. Biol., 2000, 303(5), 721-732.
[http://dx.doi.org/10.1006/jmbi.2000.4158] [PMID: 11061971]
[31]
Kaneko, K.; Chuang, V.T.; Minomo, A.; Yamasaki, K.; Bhagavan, N.V.; Maruyama, T.; Otagiri, M. Histidine146 of human serum albumin plays a prominent role at the interface of subdomains IA and IIA in allosteric ligand binding. IUBMB Life, 2011, 63(4), 277-285.
[http://dx.doi.org/10.1002/iub.457] [PMID: 21488149]
[32]
Ascenzi, P.; di Masi, A.; Leboffe, L.; Alberio, T.; Fanali, G.; Fasano, M. Molecular phylogenetic analyses of albuminoids reveal the molecular evolution of allosteric properties. IUBMB Life, 2013, 65(6), 544-549.
[http://dx.doi.org/10.1002/iub.1164] [PMID: 23568641]
[33]
Ascenzi, P.; di Masi, A.; Fanali, G.; Fasano, M. Heme-based catalytic properties of human serum albumin. Cell Death Discov., 2015, 1, 15025.
[http://dx.doi.org/10.1038/cddiscovery.2015.25] [PMID: 27551458]
[34]
di Masi, A.; Leboffe, L.; Trezza, V.; Fanali, G.; Coletta, M.; Fasano, M.; Ascenzi, P. Drugs modulate allosterically heme-Fe-recognition by human serum albumin and heme-fe-mediated reactivity. Curr. Pharm. Des., 2015, 21(14), 1837-1847.
[http://dx.doi.org/10.2174/1381612821666150302114430] [PMID: 25732555]
[35]
Bhattacharya, A.A.; Curry, S.; Franks, N.P. Binding of the general anesthetics propofol and halothane to human serum albumin. High resolution crystal structures. J. Biol. Chem., 2000, 275(49), 38731-38738.
[http://dx.doi.org/10.1074/jbc.M005460200] [PMID: 10940303]
[36]
Zunszain, P.A.; Ghuman, J.; McDonagh, A.F.; Curry, S. Crystallographic analysis of human serum albumin complexed with 4Z, 15E-bilirubin-IXalpha. J. Mol. Biol., 2008, 381(2), 394-406.
[http://dx.doi.org/10.1016/j.jmb.2008.06.016] [PMID: 18602119]
[37]
Zhu, L.; Yang, F.; Chen, L.; Meehan, E.J.; Huang, M. A new drug binding subsite on human serum albumin and drug-drug interaction studied by X-ray crystallography. J. Struct. Biol., 2008, 162(1), 40-49.
[http://dx.doi.org/10.1016/j.jsb.2007.12.004] [PMID: 18258455]
[38]
Lejon, S.; Cramer, J.F.; Nordberg, P. Structural basis for the binding of naproxen to human serum albumin in the presence of fatty acids and the GA module. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun., 2008, 64(Pt 2), 64-69.
[http://dx.doi.org/10.1107/S174430910706770X] [PMID: 18259051]
[39]
Yang, F.; Bian, C.; Zhu, L.; Zhao, G.; Huang, Z.; Huang, M. Effect of human serum albumin on drug metabolism: structural evidence of esterase activity of human serum albumin. J. Struct. Biol., 2007, 157(2), 348-355.
[http://dx.doi.org/10.1016/j.jsb.2006.08.015] [PMID: 17067818]
[40]
Sudlow, G.; Birkett, D.J.; Wade, D.N. The characterization of two specific drug binding sites on human serum albumin. Mol. Pharmacol., 1975, 11(6), 824-832.
[PMID: 1207674]
[41]
Sudlow, G.; Birkett, D.J.; Wade, D.N. Further characterization of specific drug binding sites on human serum albumin. Mol. Pharmacol., 1976, 12(6), 1052-1061.
[PMID: 1004490]
[42]
Carter, D.C.; Ho, J.X. Structure of serum albumin. Adv. Protein Chem., 1994, 45, 153-203.
[http://dx.doi.org/10.1016/S0065-3233(08)60640-3] [PMID: 8154369]
[43]
Yamasaki, K.; Maruyama, T.; Yoshimoto, K.; Tsutsumi, Y.; Narazaki, R.; Fukuhara, A.; Kragh-Hansen, U.; Otagiri, M. Interactive binding to the two principal ligand binding sites of human serum albumin: effect of the neutral-to-base transition. Biochim. Biophys. Acta, 1999, 1432(2), 313-323.
[http://dx.doi.org/10.1016/S0167-4838(99)00098-9] [PMID: 10407153]
[44]
Petitpas, I.; Bhattacharya, A.A.; Twine, S.; East, M.; Curry, S. Crystal structure analysis of warfarin binding to human serum albumin: anatomy of drug site I. J. Biol. Chem., 2001, 276(25), 22804-22809.
[http://dx.doi.org/10.1074/jbc.M100575200] [PMID: 11285262]
[45]
Hamilton, J.A. Fatty acid interactions with proteins: what X-ray crystal and NMR solution structures tell us. Prog. Lipid Res., 2004, 43(3), 177-199.
[http://dx.doi.org/10.1016/j.plipres.2003.09.002] [PMID: 15003394]
[46]
Ascenzi, P.; Tundo, G.R.; Fanali, G.; Coletta, M.; Fasano, M. Warfarin modulates the nitrite reductase activity of ferrous human serum heme-albumin. J. Biol. Inorg. Chem., 2013, 18(8), 939-946.
[http://dx.doi.org/10.1007/s00775-013-1040-2] [PMID: 24037275]
[47]
Fanali, G.; Fasano, M.; Ascenzi, P.; Zingg, J.M.; Azzi, A. α-Tocopherol binding to human serum albumin. Biofactors, 2013, 39(3), 294-303.
[http://dx.doi.org/10.1002/biof.1070] [PMID: 23355326]
[48]
Johansson, J.S.; Zou, H.; Tanner, J.W. Bound volatile general anesthetics alter both local protein dynamics and global protein stability. Anesthesiology, 1999, 90(1), 235-245.
[http://dx.doi.org/10.1097/00000542-199901000-00030] [PMID: 9915333]
[49]
Enokida, T.; Yamasaki, K.; Okamoto, Y.; Taguchi, K.; Ishiguro, T.; Maruyama, T.; Seo, H.; Otagiri, M. Tyrosine411 and Argi-nine410 of human serum albumin play an important role in the binding of sodium 4-phenylbutyrate to site II. J. Pharm. Sci., 2016, 105(6), 1987-1994.
[http://dx.doi.org/10.1016/j.xphs.2016.03.012] [PMID: 27113474]
[50]
Yamasaki, K.; Enokida, T.; Taguchi, K.; Miyamura, S.; Kawai, A.; Miyamoto, S.; Maruyama, T.; Seo, H.; Otagiri, M. Species differences in the binding of sodium 4-phenylbutyrate to serum albumin. J. Pharm. Sci., 2017, 106(9), 2860-2867.
[http://dx.doi.org/10.1016/j.xphs.2017.04.025] [PMID: 28456727]
[51]
Simard, J.R.; Zunszain, P.A.; Hamilton, J.A.; Curry, S. Location of high and low affinity fatty acid binding sites on human serum albumin revealed by NMR drug-competition analysis. J. Mol. Biol., 2006, 361(2), 336-351.
[http://dx.doi.org/10.1016/j.jmb.2006.06.028] [PMID: 16844140]
[52]
Fanali, G.; Bocedi, A.; Ascenzi, P.; Fasano, M. Modulation of heme and myristate binding to human serum albumin by anti-HIV drugs. An optical and NMR spectroscopic study. FEBS J., 2007, 274(17), 4491-4502.
[http://dx.doi.org/10.1111/j.1742-4658.2007.05978.x] [PMID: 17725715]
[53]
Fanali, G.; Cao, Y.; Ascenzi, P.; Trezza, V.; Rubino, T.; Parolaro, D.; Fasano, M. Binding of δ9-tetrahydrocannabinol and diazepam to human serum albumin. IUBMB Life, 2011, 63(6), 446-451.
[http://dx.doi.org/10.1002/iub.466] [PMID: 21557446]
[54]
Bocedi, A.; De Sanctis, G.; Ciaccio, C.; Tundo, G.R.; Di Masi, A.; Fanali, G.; Nicoletti, F.P.; Fasano, M.; Smulevich, G.; Ascenzi, P.; Coletta, M. Reciprocal allosteric modulation of carbon monoxide and warfarin binding to ferrous human serum heme-albumin. PLoS One, 2013, 8(3), e58842.
[http://dx.doi.org/10.1371/journal.pone.0058842] [PMID: 23555601]
[55]
Di Muzio, E.; Polticelli, F.; Trezza, V.; Fanali, G.; Fasano, M.; Ascenzi, P. Imatinib binding to human serum albumin modulates heme association and reactivity. Arch. Biochem. Biophys., 2014, 560, 100-112.
[http://dx.doi.org/10.1016/j.abb.2014.07.001] [PMID: 25057771]
[56]
Hawkins, D.; Pinckard, R.N.; Farr, R.S. Acetylation of human serum albumin by acetylsalicylic acid. Science, 1968, 160(3829), 780-781.
[http://dx.doi.org/10.1126/science.160.3829.780] [PMID: 5651209]
[57]
Pinckard, R.N.; Hawkins, D.; Farr, R.S. In vitro acetylation of plasma proteins, enzymes and DNA by aspirin. Nature, 1968, 219(5149), 68-69.
[http://dx.doi.org/10.1038/219068a0] [PMID: 4173352]
[58]
Hawkins, D.; Pinckard, R.N.; Crawford, I.P.; Farr, R.S. Structural changes in human serum albumin induced by ingestion of acetylsalicylic acid. J. Clin. Invest., 1969, 48(3), 536-542.
[http://dx.doi.org/10.1172/JCI106011] [PMID: 5773090]
[59]
Walker, J.E. Lysine residue 199 of human serum albumin is modified by acetylsalicyclic acid. FEBS Lett., 1976, 66(2), 173-175.
[http://dx.doi.org/10.1016/0014-5793(76)80496-6] [PMID: 955075]
[60]
Burch, J.W.; Blazer-Yost, B. Acetylation of albumin by low doses of aspirin. Thromb. Res., 1981, 23(4-5), 447-452.
[http://dx.doi.org/10.1016/0049-3848(81)90205-X] [PMID: 7324005]
[61]
Honma, K.; Nakamura, M.; Ishikawa, Y. Acetylsalicylate-human serum albumin interaction as studied by NMR spectroscopy--antigenicity-producing mechanism of acetylsalicylic acid. Mol. Immunol., 1991, 28(1-2), 107-113.
[http://dx.doi.org/10.1016/0161-5890(91)90093-Y] [PMID: 2011121]
[62]
Gresner, P.; Dolník, M.; Waczulíková, I.; Bryszewska, M.; Sikurová, L.; Watala, C. Increased blood plasma hydrolysis of acetylsalicylic acid in type 2 diabetic patients: a role of plasma esterases. Biochim. Biophys. Acta, 2006, 1760(2), 207-215.
[http://dx.doi.org/10.1016/j.bbagen.2005.11.018] [PMID: 16442234]
[63]
Petitpas, I.; Petersen, C.E.; Ha, C.E.; Bhattacharya, A.A.; Zunszain, P.A.; Ghuman, J.; Bhagavan, N.V.; Curry, S. Structural basis of albumin-thyroxine interactions and familial dysalbuminemic hyperthyroxinemia. Proc. Natl. Acad. Sci. USA, 2003, 100(11), 6440-6445.
[http://dx.doi.org/10.1073/pnas.1137188100] [PMID: 12743361]
[64]
Yang, J.; Ha, C.E.; Bhagavan, N.V. Site-directed mutagenesis study of the role of histidine residues in the neutral-to-basic transition of human serum albumin. Biochim. Biophys. Acta, 2005, 1724(1-2), 37-48.
[http://dx.doi.org/10.1016/j.bbagen.2005.03.020] [PMID: 15913893]
[65]
Esteban-Fernández, D.; Verdaguer, J.M.; Ramírez-Camacho, R.; Palacios, M.A.; Gómez-Gómez, M.M. Accumulation, fractionation, and analysis of platinum in toxicologically affected tissues after cisplatin, oxaliplatin, and carboplatin administration. J. Anal. Toxicol., 2008, 32(2), 140-146.
[http://dx.doi.org/10.1093/jat/32.2.140] [PMID: 18334097]
[66]
Will, J.; Wolters, D.A.; Sheldrick, W.S. Characterisation of cisplatin binding sites in human serum proteins using hyphenated multidimensional liquid chromatography and ESI tandem mass spectrometry. Chem. Med. Chem., 2008, 3(11), 1696-1707.
[http://dx.doi.org/10.1002/cmdc.200800151] [PMID: 18855968]
[67]
Hu, W.; Luo, Q.; Wu, K.; Li, X.; Wang, F.; Chen, Y.; Ma, X.; Wang, J.; Liu, J.; Xiong, S.; Sadler, P.J. The anticancer drug cisplatin can cross-link the interdomain zinc site on human albumin. Chem. Commun. (Camb.), 2011, 47(21), 6006-6008.
[http://dx.doi.org/10.1039/c1cc11627d] [PMID: 21526258]
[68]
Messori, L.; Merlino, A. Cisplatin binding to proteins: a structural perspective. Coord. Chem. Rev., 2016, 315, 67-89.
[http://dx.doi.org/10.1021/ic500360f]]
[69]
Diana, F.J.; Veronich, K.; Kapoor, A.L. Binding of nonsteroidal anti-inflammatory agents and their effect on binding of racemic warfarin and its enantiomers to human serum albumin. J. Pharm. Sci., 1989, 78(3), 195-199.
[http://dx.doi.org/10.1002/jps.2600780304] [PMID: 2724076]
[70]
Chuang, V.T.; Otagiri, M. How do fatty acids cause allosteric binding of drugs to human serum albumin? Pharm. Res., 2002, 19(10), 1458-1464.
[http://dx.doi.org/10.1023/A:1020496314081] [PMID: 12425462]
[71]
van der Vusse, G.J. Albumin as fatty acid transporter. Drug Metab. Pharmacokinet., 2009, 24(4), 300-307.
[http://dx.doi.org/10.2133/dmpk.24.300] [PMID: 19745557]
[72]
Yamasaki, K.; Chuang, V.T.; Maruyama, T.; Otagiri, M. Albumin-drug interaction and its clinical implication. Biochim. Biophys. Acta, 2013, 1830(12), 5435-5443.
[http://dx.doi.org/10.1016/j.bbagen.2013.05.005] [PMID: 23665585]
[73]
Otagiri, M. A molecular functional study on the interactions of drugs with plasma proteins. Drug Metab. Pharmacokinet., 2005, 20(5), 309-323.
[http://dx.doi.org/10.2133/dmpk.20.309] [PMID: 16272748]
[74]
Tesseromatis, C.; Alevizou, A. The role of the protein-binding on the mode of drug action as well the interactions with other drugs. Eur. J. Drug Metab. Pharmacokinet., 2008, 33(4), 225-230.
[http://dx.doi.org/10.1007/BF03190876] [PMID: 19230595]
[75]
Otagiri, M.; Chuang, V.T. Pharmaceutically important pre- and posttranslational modifications on human serum albumin. Biol. Pharm. Bull., 2009, 32(4), 527-534.
[http://dx.doi.org/10.1248/bpb.32.527] [PMID: 19336879]
[76]
Yang, F.; Lee, P.; Ma, Z.; Ma, L.; Yang, G.; Wu, X.; Liang, H. Regulation of amantadine hydrochloride binding with IIA subdomain of human serum albumin by fatty acid chains. J. Pharm. Sci., 2013, 102(1), 84-92.
[http://dx.doi.org/10.1002/jps.23336] [PMID: 23108589]
[77]
Spector, A.A.; Fletcher, J.E. In: Transport of fatty acid in the circulation. Disturbances in Lipid and Lipoprotein Me-tabolism; Dietschy, J.M.; Gotto, A.M; Ontko, J.A., Ed.; Bethesda American Physiological Society , 1978; pp. 229-249.
[78]
Brodersen, R.; Andersen, S.; Vorum, H.; Nielsen, S.U.; Pedersen, A.O. Multiple fatty acid binding to albumin in human blood plasma. Eur. J. Biochem., 1990, 189(2), 343-349.
[http://dx.doi.org/10.1111/j.1432-1033.1990.tb15495.x] [PMID: 2338079]
[79]
Richieri, G.V.; Kleinfeld, A.M. Unbound free fatty acid levels in human serum. J. Lipid Res., 1995, 36(2), 229-240.
[PMID: 7751810]
[80]
Simard, J.R.; Zunszain, P.A.; Ha, C.E.; Yang, J.S.; Bhagavan, N.V.; Petitpas, I.; Curry, S.; Hamilton, J.A. Locating high-affinity fatty acid-binding sites on albumin by x-ray crystallography and NMR spectroscopy. Proc. Natl. Acad. Sci. USA, 2005, 102(50), 17958-17963.
[http://dx.doi.org/10.1073/pnas.0506440102] [PMID: 16330771]
[81]
Sułkowska, A.; Bojko, B.; Równicka, J.; Sułkowski, W. Competition of drugs to serum albumin in combination therapy. Biopolymers, 2004, 74(3), 256-262.
[http://dx.doi.org/10.1002/bip.20031] [PMID: 15150801]
[82]
Seedher, N.; Kanojia, M. Fluorescence spectroscopic study for competitive binding of antidiabetic drugs and endogenous substances on serum albumin. Drug Metabol. Drug Interact., 2013, 28(2), 107-114.
[http://dx.doi.org/10.1515/dmdi-2012-0044] [PMID: 23612595]
[83]
Rolan, P.E. Plasma protein binding displacement interactions--why are they still regarded as clinically important? Br. J. Clin. Pharmacol., 1994, 37(2), 125-128.
[http://dx.doi.org/10.1111/j.1365-2125.1994.tb04251.x] [PMID: 8186058]
[84]
Kuchimanchi, K.R.; Ahmed, M.S.; Johnston, T.P.; Mitra, A.K. Binding of cosalane--a novel highly lipophilic anti-HIV agent--to albumin and glycoprotein. J. Pharm. Sci., 2001, 90(5), 659-666.
[http://dx.doi.org/10.1002/1520-6017(200105)90:5<659:AID-JPS1022>3.0.CO;2-8] [PMID: 11288110]
[85]
Cui, Y.F.; Bai, G.Y.; Li, C.G.; Ye, C.H.; Liu, M.L. Analysis of competitive binding of ligands to human serum albumin using NMR relaxation measurements. J. Pharm. Biomed. Anal., 2004, 34(2), 247-254.
[http://dx.doi.org/10.1016/S0731-7085(03)00579-X] [PMID: 15013138]
[86]
Cao, Y.; Nicoletti, F.P.; De Sanctis, G.; Bocedi, A.; Ciaccio, C.; Gullotta, F.; Fanali, G.; Tundo, G.R.; di Masi, A.; Fasano, M.; Smulevich, G.; Ascenzi, P.; Coletta, M. Evidence for pH-dependent multiple conformers in iron(II) heme-human serum albumin: spectroscopic and kinetic investigation of carbon monoxide binding. J. Biol. Inorg. Chem., 2012, 17(1), 133-147.
[http://dx.doi.org/10.1007/s00775-011-0837-0] [PMID: 21894504]
[87]
di Masi, A.; Gullotta, F.; Bolli, A.; Fanali, G.; Fasano, M.; Ascenzi, P. Ibuprofen binding to secondary sites allosterically modulates the spectroscopic and catalytic properties of human serum heme-albumin. FEBS J., 2011, 278(4), 654-662.
[http://dx.doi.org/10.1111/j.1742-4658.2010.07986.x] [PMID: 21205199]
[88]
Fanali, G.; Pariani, G.; Ascenzi, P.; Fasano, M. Allosteric and binding properties of Asp1-Glu382 truncated recombinant human serum albumin--an optical and NMR spectroscopic investigation. FEBS J., 2009, 276(8), 2241-2250.
[http://dx.doi.org/10.1111/j.1742-4658.2009.06952.x] [PMID: 19298387]
[89]
Petersen, C.E.; Ha, C.E.; Jameson, D.M.; Bhagavan, N.V. Mutations in a specific human serum albumin thyroxine binding site define the structural basis of familial dysalbuminemic hyperthyroxinemia. J. Biol. Chem., 1996, 271(32), 19110-19117.
[http://dx.doi.org/10.1074/jbc.271.32.19110] [PMID: 8702585]
[90]
Leboffe, L.; di Masi, A.; Trezza, V.; Polticelli, F.; Ascenzi, P. Human serum albumin: A modulator of cannabinoid drugs. IUBMB Life, 2017, 69(11), 834-840.
[http://dx.doi.org/10.1002/iub.1682] [PMID: 28976704]
[91]
Zunszain, P.A.; Ghuman, J.; Komatsu, T.; Tsuchida, E.; Curry, S. Crystal structural analysis of human serum albumin complexed with hemin and fatty acid. BMC Struct. Biol., 2003, 3, 6.
[http://dx.doi.org/10.1186/1472-6807-3-6] [PMID: 12846933]
[92]
Fanali, G.; Fesce, R.; Agrati, C.; Ascenzi, P.; Fasano, M. Allosteric modulation of myristate and Mn(III)heme binding to human serum albumin. Optical and NMR spectroscopy characterization. FEBS J., 2005, 272(18), 4672-4683.
[http://dx.doi.org/10.1111/j.1742-4658.2005.04883.x] [PMID: 16156788]
[93]
Nicoletti, F.P.; Howes, B.D.; Fittipaldi, M.; Fanali, G.; Fasano, M.; Ascenzi, P.; Smulevich, G. Ibuprofen induces an allosteric conformational transition in the heme complex of human serum albumin with significant effects on heme ligation. J. Am. Chem. Soc., 2008, 130(35), 11677-11688.
[http://dx.doi.org/10.1021/ja800966t] [PMID: 18681435]
[94]
Ascenzi, P.; Bocedi, A.; Notari, S.; Fanali, G.; Fesce, R.; Fasano, M. Allosteric modulation of drug binding to human serum albumin. Mini Rev. Med. Chem., 2006, 6(4), 483-489.
[http://dx.doi.org/10.2174/138955706776361448] [PMID: 16613585]
[95]
Ascenzi, P.; Fasano, M. Abacavir modulates peroxynitrite-mediated oxidation of ferrous nitrosylated human serum heme-albumin. Biochem. Biophys. Res. Commun., 2007, 353(2), 469-474.
[http://dx.doi.org/10.1016/j.bbrc.2006.12.041] [PMID: 17188651]
[96]
Meneghini, C.; Leboffe, L.; Bionducci, M.; Fanali, G.; Meli, M.; Colombo, G.; Fasano, M.; Ascenzi, P.; Mobilio, S. The five-to-six-coordination transition of ferric human serum heme-albumin is allosterically-modulated by ibuprofen and warfarin: a combined XAS and MD study. PLoS One, 2014, 9(8), e104231.
[http://dx.doi.org/10.1371/journal.pone.0104231] [PMID: 25153171]
[97]
Ascenzi, P.; Bocedi, A.; Gioia, M.; Fanali, G.; Fasano, M.; Coletta, M. Warfarin inhibits allosterically the reductive nitrosylation of ferric human serum heme-albumin. J. Inorg. Biochem., 2017, 177, 63-75.
[http://dx.doi.org/10.1016/j.jinorgbio.2017.08.030] [PMID: 28926756]
[98]
Ascenzi, P.; Colasanti, M.; Persichini, T.; Muolo, M.; Polticelli, F.; Venturini, G.; Bordo, D.; Bolognesi, M. Re-evaluation of amino acid sequence and structural consensus rules for cysteine-nitric oxide reactivity. Biol. Chem., 2000, 381(7), 623-627.
[http://dx.doi.org/10.1515/BC.2000.081] [PMID: 10987371]
[99]
Sampath, V.; Zhao, X.J.; Caughey, W.S. Anesthetic-like interactions of nitric oxide with albumin and hemeproteins. A mechanism for control of protein function. J. Biol. Chem., 2001, 276(17), 13635-13643.
[http://dx.doi.org/10.1074/jbc.M006588200] [PMID: 11278308]
[100]
Domenici, E.; Bertucci, C.; Salvadori, P.; Wainer, I.W. Use of a human serum albumin-based high-performance liquid chromatography chiral stationary phase for the investigation of protein binding: detection of the allosteric interaction between warfarin and benzodiazepine binding sites. J. Pharm. Sci., 1991, 80(2), 164-166.
[http://dx.doi.org/10.1002/jps.2600800216] [PMID: 2051322]
[101]
Fitos, I.; Simonyi, M. Stereoselective effect of phenprocoumon enantiomers on the binding of benzodiazepines to human serum albumin. Chirality, 1992, 4(1), 21-23.
[http://dx.doi.org/10.1002/chir.530040106] [PMID: 1642965]
[102]
Quinlan, G.J.; Evans, T.W.; Gutteridge, J.M. Oxidative damage to plasma proteins in adult respiratory distress syndrome. Free Radic. Res., 1994, 20(5), 289-298.
[http://dx.doi.org/10.3109/10715769409145628] [PMID: 8069386]
[103]
Anraku, M.; Kitamura, K.; Shinohara, A.; Adachi, M.; Suenga, A.; Maruyama, T.; Miyanaka, K.; Miyoshi, T.; Shiraishi, N.; Nonoguchi, H.; Otagiri, M.; Tomita, K. Intravenous iron administration induces oxidation of serum albumin in hemodialysis patients. Kidney Int., 2004, 66(2), 841-848.
[http://dx.doi.org/10.1111/j.1523-1755.2004.00813.x] [PMID: 15253741]
[104]
Anraku, M.; Kitamura, K.; Shintomo, R.; Takeuchi, K.; Ikeda, H.; Nagano, J.; Ko, T.; Mera, K.; Tomita, K.; Otagiri, M. Effect of intravenous iron administration frequency on AOPP and inflammatory biomarkers in chronic hemodialysis patients: a pilot study. Clin. Biochem., 2008, 41(14-15), 1168-1174.
[http://dx.doi.org/10.1016/j.clinbiochem.2008.07.007] [PMID: 18692036]
[105]
Himmelfarb, J.; McMonagle, E. Albumin is the major plasma protein target of oxidant stress in uremia. Kidney Int., 2001, 60(1), 358-363.
[http://dx.doi.org/10.1046/j.1523-1755.2001.00807.x] [PMID: 11422772]
[106]
Musante, L.; Bruschi, M.; Candiano, G.; Petretto, A.; Dimasi, N.; Del Boccio, P.; Urbani, A.; Rialdi, G.; Ghiggeri, G.M. Characterization of oxidation end product of plasma albumin ‘in vivo’. Biochem. Biophys. Res. Commun., 2006, 349(2), 668-673.
[http://dx.doi.org/10.1016/j.bbrc.2006.08.079] [PMID: 16949044]
[107]
Nagumo, K.; Tanaka, M.; Chuang, V.T.; Setoyama, H.; Watanabe, H.; Yamada, N.; Kubota, K.; Tanaka, M.; Matsushita, K.; Yoshida, A.; Jinnouchi, H.; Anraku, M.; Kadowaki, D.; Ishima, Y.; Sasaki, Y.; Otagiri, M.; Maruyama, T. Cys34-cysteinylated human serum albumin is a sensitive plasma marker in oxidative stress-related chronic diseases. PLoS One, 2014, 9(1), e85216.
[http://dx.doi.org/10.1371/journal.pone.0085216] [PMID: 24416365]
[108]
Anraku, M.; Kragh-Hansen, U.; Kawai, K.; Maruyama, T.; Yamasaki, Y.; Takakura, Y.; Otagiri, M. Validation of the chloramine-T induced oxidation of human serum albumin as a model for oxidative damage in vivo. Pharm. Res., 2003, 20(4), 684-692.
[http://dx.doi.org/10.1023/A:1023219420935] [PMID: 12739779]
[109]
Mera, K.; Anraku, M.; Kitamura, K.; Nakajou, K.; Maruyama, T.; Otagiri, M. The structure and function of oxidized albumin in hemodialysis patients: Its role in elevated oxidative stress via neutrophil burst. Biochem. Biophys. Res. Commun., 2005, 334(4), 1322-1328.
[http://dx.doi.org/10.1016/j.bbrc.2005.07.035] [PMID: 16054887]
[110]
Mera, K.; Anraku, M.; Kitamura, K.; Nakajou, K.; Maruyama, T.; Tomita, K.; Otagiri, M. Oxidation and carboxy methyl lysine-modification of albumin: possible involvement in the progression of oxidative stress in hemodialysis patients. Hypertens. Res., 2005, 28(12), 973-980.
[http://dx.doi.org/10.1291/hypres.28.973] [PMID: 16671336]
[111]
Oettl, K.; Stauber, R.E. Physiological and pathological changes in the redox state of human serum albumin critically influence its binding properties. Br. J. Pharmacol., 2007, 151(5), 580-590.
[http://dx.doi.org/10.1038/sj.bjp.0707251] [PMID: 17471184]
[112]
Baraka-Vidot, J.; Guerin-Dubourg, A.; Bourdon, E.; Rondeau, P. Impaired drug-binding capacities of in vitro and in vivo glycated albumin. Biochimie, 2012, 94(9), 1960-1967.
[http://dx.doi.org/10.1016/j.biochi.2012.05.017] [PMID: 22627382]
[113]
Anraku, M.; Chuang, V.T.; Maruyama, T.; Otagiri, M. Redox properties of serum albumin. Biochim. Biophys. Acta, 2013, 1830(12), 5465-5472.
[http://dx.doi.org/10.1016/j.bbagen.2013.04.036] [PMID: 23644037]
[114]
Gutteridge, J.M. Antioxidant properties of the proteins caeruloplasmin, albumin and transferrin. A study of their activity in serum and synovial fluid from patients with rheumatoid arthritis. Biochim. Biophys. Acta, 1986, 869(2), 119-127.
[http://dx.doi.org/10.1016/0167-4838(86)90286-4] [PMID: 3942755]
[115]
Christodoulou, J.; Sadler, P.J.; Tucker, A. 1H NMR of albumin in human blood plasma: drug binding and redox reactions at Cys34. FEBS Lett., 1995, 376(1-2), 1-5.
[http://dx.doi.org/10.1016/0014-5793(95)01231-2] [PMID: 8521951]
[116]
Kragh-Hansen, U.; Chuang, V.T.; Otagiri, M. Practical aspects of the ligand-binding and enzymatic properties of human serum albumin. Biol. Pharm. Bull., 2002, 25(6), 695-704.
[http://dx.doi.org/10.1248/bpb.25.695] [PMID: 12081132]
[117]
Dhubhghaill, O.M.N.; Sadler, P.J.; Tucker, A. Drug-induced reactions of bovine serum albumin: 1H NMR studies of gold binding and cysteine release. J. Am. Chem. Soc., 1992, 114, 1118-1120.
[http://dx.doi.org/10.1021/ja00029a067]
[118]
Roberts, J.R.; Xiao, J.; Schliesman, B.; Parsons, D.J.; Shaw, C.F. III Kinetics and mechanism of the reaction between serum albumin and auranofin (and its isopropyl analogue) in vitro. Inorg. Chem., 1996, 35(2), 424-433.
[http://dx.doi.org/10.1021/ic9414280] [PMID: 11666224]
[119]
Nakajou, K.; Watanabe, H.; Kragh-Hansen, U.; Maruyama, T.; Otagiri, M. The effect of glycation on the structure, function and biological fate of human serum albumin as revealed by recombinant mutants. Biochim. Biophys. Acta, 2003, 1623(2-3), 88-97.
[http://dx.doi.org/10.1016/j.bbagen.2003.08.001] [PMID: 14572906]
[120]
Anguizola, J.A.; Basiaga, S.B.; Hage, D.S. Effects of fatty acids and glycation on drug interactions with human serum albumin. Curr. Metabolomics, 2013, 1(3), 239-250.
[http://dx.doi.org/10.2174/2213235X1130100005] [PMID: 24349966]
[121]
Mereish, K.A.; Rosenberg, H.; Cobby, J. Glucosylated albumin and its influence on salicylate binding. J. Pharm. Sci., 1982, 71(2), 235-238.
[http://dx.doi.org/10.1002/jps.2600710223] [PMID: 7062252]
[122]
Okabe, N.; Hashizume, N. Drug binding properties of glycosylated human serum albumin as measured by fluorescence and circular dichroism. Biol. Pharm. Bull., 1994, 17(1), 16-21.
[http://dx.doi.org/10.1248/bpb.17.16] [PMID: 8148809]
[123]
Shaklai, N.; Garlick, R.L.; Bunn, H.F. Nonenzymatic glycosylation of human serum albumin alters its conformation and function. J. Biol. Chem., 1984, 259(6), 3812-3817.
[PMID: 6706980]
[124]
Gajahi Soudahome, A.; Catan, A.; Giraud, P.; Assouan Kouao, S.; Guerin-Dubourg, A.; Debussche, X.; Le Moullec, N.; Bourdon, E.; Bravo, S.B.; Paradela-Dobarro, B.; Álvarez, E.; Meilhac, O.; Rondeau, P.; Couprie, J. Glycation of human serum albumin impairs binding to the glucagon-like peptide-1 analogue liraglutide. J. Biol. Chem., 2018, 293(13), 4778-4791.
[http://dx.doi.org/10.1074/jbc.M117.815274] [PMID: 29414771]
[125]
Tsuchiya, S.; Sakurai, T.; Sekiguchi, S. Nonenzymatic glucosylation of human serum albumin and its influence on binding capacity of sulfonylureas. Biochem. Pharmacol., 1984, 33(19), 2967-2971.
[http://dx.doi.org/10.1016/0006-2952(84)90595-1] [PMID: 6487349]
[126]
Joseph, K.S.; Anguizola, J.; Jackson, A.J.; Hage, D.S. Chromatographic analysis of acetohexamide binding to glycated human serum albumin. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2010, 878(28), 2775-2781.
[http://dx.doi.org/10.1016/j.jchromb.2010.08.021] [PMID: 20829128]
[127]
Joseph, K.S.; Hage, D.S. Characterization of the binding of sulfonylurea drugs to HSA by high-performance affinity chromatography. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2010, 878(19), 1590-1598.
[http://dx.doi.org/10.1016/j.jchromb.2010.04.019] [PMID: 20435530]
[128]
Joseph, K.S.; Anguizola, J.; Hage, D.S. Binding of tolbutamide to glycated human serum albumin. J. Pharm. Biomed. Anal., 2011, 54(2), 426-432.
[http://dx.doi.org/10.1016/j.jpba.2010.09.003] [PMID: 20880646]
[129]
Matsuda, R.; Anguizola, J.; Joseph, K.S.; Hage, D.S. High-performance affinity chromatography and the analysis of drug interactions with modified proteins: binding of gliclazide with glycated human serum albumin. Anal. Bioanal. Chem., 2011, 401(9), 2811-2819.
[http://dx.doi.org/10.1007/s00216-011-5382-8] [PMID: 21922305]
[130]
Matsuda, R.; Anguizola, J.; Joseph, K.S.; Hage, D.S. Analysis of drug interactions with modified proteins by high-performance affinity chromatography: binding of glibenclamide to normal and glycated human serum albumin. J. Chromatogr. A, 2012, 1265, 114-122.
[http://dx.doi.org/10.1016/j.chroma.2012.09.091] [PMID: 23092871]
[131]
Anguizola, J.; Joseph, K.S.; Barnaby, O.S.; Matsuda, R.; Alvarado, G.; Clarke, W.; Cerny, R.L.; Hage, D.S. Development of affinity microcolumns for drug-protein binding studies in personalized medicine: interactions of sulfonylurea drugs with in vivo glycated human serum albumin. Anal. Chem., 2013, 85(9), 4453-4460.
[http://dx.doi.org/10.1021/ac303734c] [PMID: 23544441]
[132]
Jackson, A.J.; Anguizola, J.; Pfaunmiller, E.L.; Hage, D.S. Use of entrapment and high-performance affinity chromatography to compare the binding of drugs and site-specific probes with normal and glycated human serum albumin. Anal. Bioanal. Chem., 2013, 405(17), 5833-5841.
[http://dx.doi.org/10.1007/s00216-013-6981-3] [PMID: 23657448]
[133]
Anguizola, J.; Matsuda, R.; Barnaby, O.S.; Hoy, K.S.; Wa, C.; DeBolt, E.; Koke, M.; Hage, D.S. Review: glycation of human serum albumin. Clin. Chim. Acta, 2013, 425, 64-76.
[http://dx.doi.org/10.1016/j.cca.2013.07.013] [PMID: 23891854]
[134]
Rabbani, N.; Tabrez, S.; Islam, B.U.; Rehman, M.T.; Alsenaidy, A.M.; Al Ajmi, M.F.; Khan, R.A.; Alsenaidy, M.A.; Khan, M.S. Characterization of colchicine binding with normal and glycated albumin: in vitro and molecular docking analysis. J. Biomol. Struct. Dyn., 2017, 30, 1-10.
[http://dx.doi.org/10.1080/07391102.2017.1389661]] [PMID: 28990867]
[135]
Grandison, M.K.; Boudinot, F.D. Age-related changes in protein binding of drugs: implications for therapy. Clin. Pharmacokinet., 2000, 38(3), 271-290.
[http://dx.doi.org/10.2165/00003088-200038030-00005] [PMID: 10749520]
[136]
Larsen, M.T.; Kuhlmann, M.; Hvam, M.L.; Howard, K.A. Albumin-based drug delivery: harnessing nature to cure disease. Mol. Cell. Ther., 2016, 4, 3.
[http://dx.doi.org/10.1186/s40591-016-0048-8] [PMID: 26925240]
[137]
Kratz, F. DOXO-EMCH (INNO-206): the first albumin-binding prodrug of doxorubicin to enter clinical trials. Expert Opin. Investig. Drugs, 2007, 16(6), 855-866.
[http://dx.doi.org/10.1517/13543784.16.6.855] [PMID: 17501697]
[138]
Kratz, F. Albumin as a drug carrier: design of prodrugs, drug conjugates and nanoparticles. J. Control. Release, 2008, 132(3), 171-183.
[http://dx.doi.org/10.1016/j.jconrel.2008.05.010] [PMID: 18582981]
[139]
Pettersen, E.F.; Goddard, T.D.; Huang, C.C.; Couch, G.S.; Greenblatt, D.M.; Meng, E.C.; Ferrin, T.E. UCSF Chimera--a visualization system for exploratory research and analysis. J. Comput. Chem., 2004, 25(13), 1605-1612.
[http://dx.doi.org/10.1002/jcc.20084] [PMID: 15264254]

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