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Letters in Drug Design & Discovery

Editor-in-Chief

ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

Research Article

Design, Synthesis and Bioactivity of Core 1 O-glycan and its Derivative on Human Gut Microbiota

Author(s): Huanhuan Qu*, Baixue Li, Jingyi Yang, Huaiwen Liang, Meixia Li and Kan Ding*

Volume 16, Issue 12, 2019

Page: [1348 - 1353] Pages: 6

DOI: 10.2174/1570180816666181218143207

Price: $65

Abstract

Background: Disaccharide core 1 (Galβ1-3GalNAc) is a common O-glycan structure in nature. Biochemical studies have confirmed that the formation of the core 1 structure is an important initial step in O-glycan biosynthesis and it is of great importance for human body.

Objective: Our study will provide meaningful and useful sights for O-glycan synthesis and their bioassay. And all the synthetic glycosides would be used as intermediate building blocks in the scheme developed for oligosaccharide construction.

Methods: In this article, we firstly used chemical procedures to prepare core 1 and its derivative, and a novel disaccharide was efficiently synthesized. The structures of the synthesized compounds were elucidated and confirmed by 1H NMR, 13C NMR and MS. Then we employed three human gut symbionts belonging to Bacteroidetes, a predominantphyla in the distal gut, as models to study the bioactivity of core 1 and its derivative on human gut microbiota.

Results: According to our results, both core 1 and derivative could support the growth of B. fragilis, especially the core 1 derivative, while failed to support the growth of B. thetaiotaomicron and B. ovatus.

Conclusion: This suggested that the B. fragilis might have the specificity glycohydrolase to cut the glycosidic bond for acquiring monosaccharide.

Keywords: Bioactivity, core 1, derivative, human gut microbiota, O-glycan, synthesis.

Graphical Abstract
[1]
Haltiwanger, R.S.; Lowe, J.B. Role of glycosylation in development. [Review] Annu. Rev. Biochem., 2004, 73, 491-537.
[http://dx.doi.org/10.1146/annurev.biochem.73.011303.074043] [PMID: 15189151]
[2]
Brockhausen, I.; Schachter, H.; Stanley, P. Essentials of Glycobiology; Varki, A.; Cummings, R.D; Esko, J.D., Ed.; New York, 2009.
[3]
Lin, Y.R.; Reddy, B.V.; Irvine, K.D. Requirement for a core 1 galactosyltransferase in the Drosophila nervous system. Dev. Dyn., 2008, 237(12), 3703-3714.
[http://dx.doi.org/10.1002/dvdy.21775] [PMID: 18985719]
[4]
Luther, K.B.; Haltiwanger, R.S. Role of unusual O-glycans in intercellular signaling. Int. J. Biochem. Cell Biol., 2009, 41(5), 1011-1024.
[http://dx.doi.org/10.1016/j.biocel.2008.10.001] [PMID: 18952191]
[5]
Mechref, Y. Analysis of glycans derived from glycoconjugates by capillary electrophoresis-mass spectrometry. Electrophoresis, 2011, 32(24), 3467-3481.
[http://dx.doi.org/10.1002/elps.201100342] [PMID: 22180203]
[6]
Afrouziyeh, M.; Hanifian, S.; Taghinejad, M. Effects of mannan oligosaccharides on ileal digestibility of nutrients and microbial populations in the ceca of broiler chickens. Int. J. Biosci., 2014, 5(1), 373-380.
[http://dx.doi.org/10.12692/ijb/5.1.373-380]
[7]
Steentoft, C.; Vakhrushev, S.Y.; Joshi, H.J.; Kong, Y.; Vester-Christensen, M.B.; Schjoldager, K.T.; Lavrsen, K.; Dabelsteen, S.; Pedersen, N.B.; Marcos-Silva, L.; Gupta, R.; Bennett, E.P.; Mandel, U.; Brunak, S.; Wandall, H.H.; Levery, S.B.; Clausen, H. Precision mapping of the human O-GalNAc glycoproteome through SimpleCell technology. EMBO J., 2013, 32(10), 1478-1488.
[http://dx.doi.org/10.1038/emboj.2013.79] [PMID: 23584533]
[8]
Fujita, K.; Oura, F.; Nagamine, N.; Katayama, T.; Hiratake, J.; Sakata, K.; Kumagai, H.; Yamamoto, K. Identification and molecular cloning of a novel glycoside hydrolase family of core 1 type O-glycan-specific endo-α-N-acetylgalactosaminidase from Bifidobacterium longum. J. Biol. Chem., 2005, 280(45), 37415-37422.
[http://dx.doi.org/10.1074/jbc.M506874200] [PMID: 16141207]
[9]
Boons, G.J. Strategies in oligosaccharide synthesis. Tetrahedron, 1996, 52(4), 1095-1121.
[http://dx.doi.org/10.1016/0040-4020(95)00897-7]
[10]
Gerken, T.A. Kinetic modeling confirms the biosynthesis of mucin core 1 (beta-Gal(1-3) alpha-GalNAc-O-Ser/Thr) O-glycan structures are modulated by neighboring glycosylation effects. Biochemistry, 2004, 43(14), 4137-4142.
[http://dx.doi.org/10.1021/bi036306a] [PMID: 15065856]
[11]
Marciello, M.; Filice, M. Enzymatic synthesis of oligosaccharides: A powerful tool for a sweet challenge. Curr. Org. Chem., 2013, 17(7), 701-718.
[http://dx.doi.org/10.2174/1385272811317070006]
[12]
Vulevic, J.; Juric, A.; Walton, G.E.J.; Claus, S.P.; Tzortzis, G.; Toward, R.E.; Gibson, G.R. Influence of galacto-oligosaccharide mixture (B-GOS) on gut microbiota, immune parameters and metabonomics in elderly persons. Br. J. Nutr., 2015, 114(4), 586-595.
[http://dx.doi.org/10.1017/S0007114515001889] [PMID: 26218845]
[13]
Holmén Larsson, J.M.; Thomsson, K.A.; Rodríguez-Piñeiro, A.M.; Karlsson, H.; Hansson, G.C. Studies of mucus in mouse stomach, small intestine, and colon. III. Gastrointestinal Muc5ac and Muc2 mucin O-glycan patterns reveal a regiospecific distribution. Am. J. Physiol. Gastrointest. Liver Physiol., 2013, 305(5), G357-G363.
[http://dx.doi.org/10.1152/ajpgi.00048.2013] [PMID: 23832516]
[14]
Li, X.J.; Piao, X.S.; Kim, S.W.; Liu, P.; Wang, L.; Shen, Y.B.; Jung, S.C.; Lee, H.S. Effects of chito-oligosaccharide supplementation on performance, nutrient digestibility, and serum composition in broiler chickens. Poult. Sci., 2007, 86(6), 1107-1114.
[http://dx.doi.org/10.1093/ps/86.6.1107] [PMID: 17495080]
[15]
Huang, R.L.; Yin, Y.L.; Wu, G.Y.; Zhang, Y.G.; Li, T.J.; Li, L.L.; Li, M.X.; Tang, Z.R.; Zhang, J.; Wang, B.; He, J.H.; Nie, X.Z. Effect of dietary oligochitosan supplementation on ileal digestibility of nutrients and performance in broilers. Poult. Sci., 2005, 84(9), 1383-1388.
[http://dx.doi.org/10.1093/ps/84.9.1383] [PMID: 16206559]
[16]
Denev, S.A.; Dinev, I.; Nikiforov, I.; Koinarski, V. Effects of mannanoligosaccharides on composition of the cecal microflora and performance of broiler chickens; ESPN, 2005, pp. 365-367.
[17]
Rosen, G.D. Holo-analysis of the efficacy of Bio-Mos in broiler nutrition. Br. Poult. Sci., 2007, 48(1), 21-26.
[http://dx.doi.org/10.1080/00071660601050755] [PMID: 17364536]
[18]
Dr, U.H. Dipl.-Chem, J.O.; Dr, H.K. Carbohydrate scaffolds for combinatorial syntheses that allow selective deprotection of all four positions independent of the sequence. Angew. Chem. Int. Ed., 2004, 43(9), 1104-1107.
[http://dx.doi.org/10.1002/anie.200352919]
[19]
Yoshitaka, I.; Lee, R.T.; Yuan, C.L. Synthesis and binding activity of 3- and 4-deoxy-N-acetyl-galactosamine derivatives. J. Carbohydr. Chem., 1990, 9(5), 707-719.
[http://dx.doi.org/10.1080/07328309008543865]
[20]
Tomoya, O.; Kazuo, B. Synthesis of 3- O -(2-acetamido-2-deoxy-3- O -β- d -galactopyranosyl-β- d -galactopyranosyl)-1,2-di- O -tetradecyl- sn -glycerol. Carbohydr. Res., 1982, 101(2), 271-277.
[http://dx.doi.org/10.1016/S0008-6215(00)81007-1] [PMID: 7116361]
[21]
Yeom, C.E.; Lee, S.Y.; Kim, Y.J.; Kim, B.M. Mild and chemoselective deacetylation method using a catalytic amount of acetyl chloride in methanol. ChemInform, 2005, 2005(10), 1527-1530.
[http://dx.doi.org/10.1002/chin.200547055]
[22]
Feng, F.; Okuyama, K.; Niikura, K.; Ohta, T.; Sadamoto, R.; Monde, K.; Noguchi, T.; Nishimura, S. Chemo-enzymatic synthesis of fluorinated 2-N-acetamidosugar nucleotides using UDP-GlcNAc pyrophosphorylase. Org. Biomol. Chem., 2004, 2(11), 1617-1623.
[http://dx.doi.org/10.1039/b402860k] [PMID: 15162214]
[23]
Vauzeilles, B.; Baron, A.; Pons, M.J.; Fourmois, L. Method of preparation of 6-azido-2,4-diacetamido-2,4,6-trideoxy-d-m annose Eur. Pat. Appl EP3170832,, 2017.
[24]
Ohtsuka, I.; Sadakane, Y.; Hada, N.; Higuchi, M.; Atsumi, T.; Kakiuchi, N. The development of new molecular tools containing a chemically synthesized carbohydrate ligand for the elucidation of carbohydrate roles via photoaffinity labeling: Carbohydrate-protein interactions are affected by the structures of the glycosidic bonds and the reducing-end sugar. Bioorg. Med. Chem., 2014, 22(15), 3829-3837.
[http://dx.doi.org/10.1016/j.bmc.2014.06.049] [PMID: 25012569]
[25]
Mukhopadhyay, B.; Roy, N. Synthesis of the pentasaccharide related to the repeating unit of the antigen from Shigella dysenteriae type 4 in the form of its methyl ester 2-(trimethylsilyl)ethyl glycoside. Carbohydr. Res., 2003, 338(7), 589-596.
[http://dx.doi.org/10.1016/S0008-6215(02)00499-8] [PMID: 12644371]
[26]
Craft, K.M.; Townsend, S.D. Synthesis of lacto-N-tetraose. Carbohydr. Res., 2017, 440-441, 43-50.
[http://dx.doi.org/10.1016/j.carres.2017.02.001] [PMID: 28214389]
[27]
Lu, D.; Hu, Y.; He, X.; Sollogoub, M.; Zhang, Y. Total synthesis of a sialyl Lewis(x) derivative for the diagnosis of cancer. Carbohydr. Res., 2014, 383(1), 89-96.
[http://dx.doi.org/10.1016/j.carres.2013.11.012] [PMID: 24333940]
[28]
Zhang, Y.; Dong, D.; Zhou, T.; Zhang, Y.M. Study of carbohydrate–carbohydrate interactions: Total synthesis of 6d-deoxy Lewis pentaosyl glycosphingolipid. Tetrahedron, 2010, 66(37), 7373-7383.
[http://dx.doi.org/10.1016/j.tet.2010.07.025]
[29]
Zhang, G.; Guan, Z.; Zhang, L.; Min, J.; Zhang, L. Synthesis of 2-amino-2-deoxy-beta-glycosyl-(1-->5)-nucleosides and the interaction with RNA. Bioorg. Med. Chem., 2003, 11(15), 3273-3278.
[http://dx.doi.org/10.1016/S0968-0896(03)00278-5] [PMID: 12837537]
[30]
Koropatkin, N.M.; Martens, E.C.; Gordon, J.I.; Smith, T.J. Starch catabolism by a prominent human gut symbiont is directed by the recognition of amylose helices. Structure, 2008, 16(7), 1105-1115.
[http://dx.doi.org/10.1016/j.str.2008.03.017] [PMID: 18611383]
[31]
Baek, M.G.; Roy, R. Synthesis and protein binding properties of T-antigen containing GlycoPAMAM dendrimers. Bioorg. Med. Chem., 2002, 10(1), 11-17.
[http://dx.doi.org/10.1016/S0968-0896(01)00248-6] [PMID: 11738602]
[32]
Li, L.; Liu, Y.; Li, T.; Wang, W.; Yu, Z.; Ma, C.; Qu, J.; Zhao, W.; Chen, X.; Wang, P.G. Efficient chemoenzymatic synthesis of novel galacto-N-biose derivatives and their sialylated forms. Chem. Commun. (Camb.), 2015, 51(51), 10310-10313.
[http://dx.doi.org/10.1039/C5CC03746H] [PMID: 26023910]
[33]
Mazmanian, S.K.; Liu, C.H.; Tzianabos, A.O.; Kasper, D.L. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell, 2005, 122(1), 107-118.
[http://dx.doi.org/10.1016/j.cell.2005.05.007] [PMID: 16009137]

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