Identification of α-Galactosyl Epitope Mimetics through Rapid Generation and Screening of C-Linked Glycopeptide Library
| Autor: | Ming Xian, Zakia Fatima, Wei Zhang, Tracy I. Stevenson, Dehua Pei, Peng George Wang, Jianwen Fang, Hanfen Li, Joseph A. Loo |
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| Rok vydání: | 2003 |
| Předmět: |
Magnetic Resonance Spectroscopy
Oligosaccharides Enzyme-Linked Immunosorbent Assay Peptide Crystallography X-Ray Epitope Epitopes chemistry.chemical_compound Peptide Library Animals Combinatorial Chemistry Techniques Humans Moiety Peptide sequence chemistry.chemical_classification biology Glycopeptides Galactose General Chemistry Mass spectrometric Glycopeptide Immunoglobulin A Carbohydrate Sequence Immunoglobulin M chemistry Biochemistry Immunoglobulin G Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization biology.protein Indicators and Reagents Antibody |
| Zdroj: | Journal of Combinatorial Chemistry. 6:126-134 |
| ISSN: | 1520-4774 1520-4766 |
| DOI: | 10.1021/cc030042u |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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