Chemoenzymatic Assembly of Mammalian O-Mannose Glycans

Overview

Journal Angew Chem Int Ed Engl

Specialty Chemistry

Date 2018 May 27

PMID 29802667

Citations 14

Authors

Caicai Meng

Aniruddha Sasmal

Yan Zhang

Tian Gao

Chang-Cheng Liu

Naazneen Khan

Ajit Varki

Fengshan Wang

Hongzhi Cao

Affiliations

Soon will be listed here.

Abstract

O-Mannose glycans account up to 30 % of total O-glycans in the brain. Previous synthesis and functional studies have only focused on the core M3 O-mannose glycans of α-dystroglycan, which are a causative factor for various muscular diseases. In this study, a highly efficient chemoenzymatic strategy was developed that enabled the first collective synthesis of 63 core M1 and core M2 O-mannose glycans. This chemoenzymatic strategy features the gram-scale chemical synthesis of five judiciously designed core structures, and the diversity-oriented modification of the core structures with three enzyme modules to provide 58 complex O-mannose glycans in a linear sequence that does not exceed four steps. The binding profiles of synthetic O-mannose glycans with a panel of lectins, antibodies, and brain proteins were also explored by using a printed O-mannose glycan array.

Citing Articles

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References

Yu H, Chokhawala H, Karpel R, Yu H, Wu B, Zhang J . A multifunctional Pasteurella multocida sialyltransferase: a powerful tool for the synthesis of sialoside libraries. J Am Chem Soc. 2005; 127(50):17618-9. DOI: 10.1021/ja0561690. View

Esser A, Miller M, Huang Q, Meier M, de Bernabe D, Stipp C . Loss of LARGE2 disrupts functional glycosylation of α-dystroglycan in prostate cancer. J Biol Chem. 2012; 288(4):2132-42. PMC: 3554886. DOI: 10.1074/jbc.M112.432807. View

Chen X, Fang J, Zhang J, Liu Z, Shao J, Kowal P . Sugar nucleotide regeneration beads (superbeads): a versatile tool for the practical synthesis of oligosaccharides. J Am Chem Soc. 2001; 123(9):2081-2. DOI: 10.1021/ja005738v. View

Ragni E, Lommel M, Moro M, Crosti M, Lavazza C, Parazzi V . Protein O-mannosylation is crucial for human mesencyhmal stem cells fate. Cell Mol Life Sci. 2015; 73(2):445-58. PMC: 11108538. DOI: 10.1007/s00018-015-2007-y. View

Muthana M, Qu J, Li Y, Zhang L, Yu H, Ding L . Efficient one-pot multienzyme synthesis of UDP-sugars using a promiscuous UDP-sugar pyrophosphorylase from Bifidobacterium longum (BLUSP). Chem Commun (Camb). 2012; 48(21):2728-30. DOI: 10.1039/c2cc17577k. View

Dobson C, Hempel S, Stalnaker S, Stuart R, Wells L . O-Mannosylation and human disease. Cell Mol Life Sci. 2012; 70(16):2849-57. PMC: 3984002. DOI: 10.1007/s00018-012-1193-0. View

Chai W, Yuen C, Kogelberg H, Carruthers R, Margolis R, Feizi T . High prevalence of 2-mono- and 2,6-di-substituted manol-terminating sequences among O-glycans released from brain glycopeptides by reductive alkaline hydrolysis. Eur J Biochem. 1999; 263(3):879-88. DOI: 10.1046/j.1432-1327.1999.00572.x. View

Sheikh M, Halmo S, Wells L . Recent advancements in understanding mammalian O-mannosylation. Glycobiology. 2017; 27(9):806-819. PMC: 6082599. DOI: 10.1093/glycob/cwx062. View

Praissman J, Wells L . Mammalian O-mannosylation pathway: glycan structures, enzymes, and protein substrates. Biochemistry. 2014; 53(19):3066-78. PMC: 4033628. DOI: 10.1021/bi500153y. View

10.

Mo K, Fang T, Stalnaker S, Kirby P, Liu M, Wells L . Synthetic, structural, and biosynthetic studies of an unusual phospho-glycopeptide derived from α-dystroglycan. J Am Chem Soc. 2011; 133(36):14418-30. PMC: 3176502. DOI: 10.1021/ja205473q. View

11.

Sugiarto G, Lau K, Qu J, Li Y, Lim S, Mu S . A sialyltransferase mutant with decreased donor hydrolysis and reduced sialidase activities for directly sialylating LewisX. ACS Chem Biol. 2012; 7(7):1232-40. PMC: 3521065. DOI: 10.1021/cb300125k. View

12.

Endo T . Glycobiology of α-dystroglycan and muscular dystrophy. J Biochem. 2014; 157(1):1-12. DOI: 10.1093/jb/mvu066. View

13.

Imperiali M, Thoma C, Pavoni E, Brancaccio A, Callewaert N, Oxenius A . O Mannosylation of alpha-dystroglycan is essential for lymphocytic choriomeningitis virus receptor function. J Virol. 2005; 79(22):14297-308. PMC: 1280192. DOI: 10.1128/JVI.79.22.14297-14308.2005. View

14.

Dwyer C, Katoh T, Tiemeyer M, Matthews R . Neurons and glia modify receptor protein-tyrosine phosphatase ζ (RPTPζ)/phosphacan with cell-specific O-mannosyl glycans in the developing brain. J Biol Chem. 2015; 290(16):10256-73. PMC: 4400340. DOI: 10.1074/jbc.M114.614099. View

15.

Lau K, Thon V, Yu H, Ding L, Chen Y, Muthana M . Highly efficient chemoenzymatic synthesis of beta1-4-linked galactosides with promiscuous bacterial beta1-4-galactosyltransferases. Chem Commun (Camb). 2010; 46(33):6066-8. PMC: 3114949. DOI: 10.1039/c0cc01381a. View

16.

Wang W, Hu T, Frantom P, Zheng T, Gerwe B, Del Amo D . Chemoenzymatic synthesis of GDP-L-fucose and the Lewis X glycan derivatives. Proc Natl Acad Sci U S A. 2009; 106(38):16096-101. PMC: 2752511. DOI: 10.1073/pnas.0908248106. View

17.

Praissman J, Willer T, Sheikh M, Toi A, Chitayat D, Lin Y . The functional O-mannose glycan on α-dystroglycan contains a phospho-ribitol primed for matriglycan addition. Elife. 2016; 5. PMC: 4924997. DOI: 10.7554/eLife.14473. View

18.

Yao W, Yan J, Chen X, Wang F, Cao H . Chemoenzymatic synthesis of lacto-N-tetrasaccharide and sialyl lacto-N-tetrasaccharides. Carbohydr Res. 2014; 401:5-10. DOI: 10.1016/j.carres.2014.10.017. View

19.

Yu J, Westerlind U . Synthesis of a glycopeptide vaccine conjugate for induction of antibodies recognizing O-mannosyl glycopeptides. Chembiochem. 2014; 15(7):939-45. DOI: 10.1002/cbic.201300537. View

20.

Gerin I, Ury B, Breloy I, Bouchet-Seraphin C, Bolsee J, Halbout M . ISPD produces CDP-ribitol used by FKTN and FKRP to transfer ribitol phosphate onto α-dystroglycan. Nat Commun. 2016; 7:11534. PMC: 4873967. DOI: 10.1038/ncomms11534. View