Comparison of the anti-amyloidogenic effect of O-mannosylation, O-galactosylation, and O-GalNAc glycosylation

详细信息    查看全文

• 作者：Chen Lin^a ; Eric H.-L. Chen^a ; Lily Y.-L. Lee^a ; Ruei-Lin Hsu^a ; Frederick Y. Luh^a ; Li-ling Yang^b ; Chia-Fu Chou^b ; Li-De Huang^c ; Chun-Cheng Lin^c ; Rita P.-Y. Chen^a ; ^d ; ^{pyc@gate.sinica.edu.tw" class="auth_mail}
• 关键词：PrP(108&ndash ; 144) ; hamster prion protein sequence 108&ndash ; 144 ; 伪-GalNAc ; 伪-N-acetylgalactosamine ; 伪-Gal ; 伪-galactose ; 伪-Man ; 伪-mannose ; PMB ; p-methoxybenzyl ; S135-伪-GalNAc ; PrP(108&ndash ; 144) with Ser135 chemically modified with an 伪-GalNAc ; S135-伪-Gal ; PrP(108&ndash ; 144) with Ser135 chemically modified with an 伪-Gal ; S135-伪-Man ; PrP(108&ndash ; 144) with Ser135 chemically modified with an 伪-Man
• 刊名：Carbohydrate Research
• 出版年：31 March, 2014
• 年：2014
• 卷：387
• 期：Complete
• 页码：46-53
• 全文大小：2736 K

文摘

Our aim was to explore the effects of functional groups at carbon-2 (C2) of a sugar on the conformational properties of the peptide backbone. Three monosaccharides, mannose, galactose, and N-acetylgalactosamine (GalNAc), were added separately to the serine side-chain of a hamster prion peptide because it is a sensitive model for comparing the effect of protein modification on the conformational properties of the polypeptide chain. In buffer, this prion peptide goes through a gradual coil-to-尾 structural conversion and forms amyloid fibrils slowly during incubation. Our results showed that a sugar with an N-acetyl amino group in the equatorial configuration (GalNAc) or with a hydroxyl group in the axial configuration (mannose) on C2 had a greater inhibitory effect on the amyloidogenesis of the prion peptide than a sugar with the hydroxyl group in the equatorial configuration (galactose). We suggest that galactosylation has less effect than mannosylation or GalNAc glycosylation on promoting turn formation at the glycosylation site and on inhibition of amyloidogenesis. The anti-amyloidogenic property of mannose implies that protein mannosylation has an anti-aggregation function.