Peptide mimicking sialyl-Lewis(a) with anti-inflammatory activity.
Peptides mimicking carbohydrate structure sialyl-Lewis a (SA-Le(a)) have been selected from a diverse dodecapeptide library using monoclonal antibody (MAb) NS19-9. Families of peptides with a consensus sequence consisting of three to nine amino acids and peptides that do not show a conserved core amino acid region were identified. Peptide DLWDWVVGKPAG was selected based on the consensus sequence DXXDXXVG shared with other peptides and strong binding in Western blot. Peptide competes with antibody binding to its native carbohydrate antigen, SA-Le(a), at 50% inhibitory concentration (IC(50)), 700 microM, implying that it represents a structural mimic of the carbohydrate epitope recognized by MAb. Statistically significant reduction of neutrophil recruitment into the intraperitoneal cavity was observed upon administration of this peptide in a murine acute inflammation model in vivo. Results suggest that the peptide mimic of SA-Le(a) carbohydrate might bind to E-selectin and block its interaction with another ligand, sialyl-Lewis X (SA-LeX), expressed on neutrophils.
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The Wistar Institute, Philadelphia, Pennsylvania, 19104, USA.
Kieber-Emmons
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Otvos
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Blaszczyk-Thurin
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D000595:Amino Acid Sequence; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D000911:Antibodies, Monoclonal; D001667:Binding, Competitive; D002240:Carbohydrate Sequence; D004195:Disease Models, Animal; D019040:E-Selectin / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D009844:Oligosaccharides / Q000737:chemistry* / Q000378:metabolism; D019151:Peptide Library; D000080506:Sialyl Lewis X Antigen
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D019040:E-Selectin; D008024:Ligands; D009842:Oligopeptides; D009844:Oligosaccharides; D019151:Peptide Library; D000080506:Sialyl Lewis X Antigen