Journal article
Identification of alpha-galactosyl epitope mimetics through rapid generation and screening of C-linked glycopeptide library
Journal of combinatorial chemistry, Vol.6(1), pp.126-134
01/2004
Handle:
https://hdl.handle.net/2376/115381
PMID: 14714996
Abstract
A general methodology has been established for rapid generation and screening of combinatorial glycopeptide library and subsequent mass spectrometric sequencing to identify the mimetics of Galalpha(1,3)Gal epitopes. Using this approach, several active glycopeptide sequences were recognized and found to inhibit the binding of human natural anti-Gal antibodies with comparable IC(50)s to synthetic Galalpha(1,3)Gal oligosaccharides. The most active glycopeptides detected from the library included Gal-Tyr-Trp-Arg-Tyr, Gal-Thr-Trp-Arg-Tyr, and Gal-Arg-Trp-Arg-Tyr. These glycopeptides showed higher affinities to anti-Gal antibodies than known Galalpha(1,3)Gal peptide mimetics, such as DAHWESWL and SSLRGF. Our results suggest that, by combining a peptide sequence (the "functional" mimic part) with a terminal alpha-linked galactose moiety (the "structural" mimic part), the resulting glycopeptide could be a very good Galalpha(1,3)Gal mimetic. Analysis of these active glycopeptides provided first-hand information regarding the binding site of anti-Gal antibodies to facilitate the structurally based design of more potent and stable inhibitors.
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Details
- Title
- Identification of alpha-galactosyl epitope mimetics through rapid generation and screening of C-linked glycopeptide library
- Creators
- Ming Xian - Department of Biochemistry and Department of Chemistry, The Ohio State University, Columbus, Ohio 43210, USAZakia FatimaWei ZhangJianwen FangHanfen LiDehua PeiJoseph LooTracy StevensonPeng George Wang
- Publication Details
- Journal of combinatorial chemistry, Vol.6(1), pp.126-134
- Academic Unit
- Department of Chemistry
- Publisher
- United States
- Grant note
- GM 54074 / NIGMS NIH HHS GM 54073 / NIGMS NIH HHS
- Identifiers
- 99900547999701842
- Language
- English
- Resource Type
- Journal article