Utilization of sialic acid-binding synthetic peptide sequences derived from pertussis toxin as novel anti-inflammatory agents
| Autor: | Glen D. Armstrong, Louis D. Heerze, Richard H. Smith, Nandi Wang |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Bordetella pertussis
Neutrophils Molecular Sequence Data Biotin Sialic acid binding Pertussis toxin Binding Competitive Biochemistry Mice chemistry.chemical_compound Lectins Animals Hypersensitivity Delayed Amino Acid Sequence Virulence Factors Bordetella Peptide sequence Inflammation Mice Inbred BALB C biology Anti-Inflammatory Agents Non-Steroidal Serum Albumin Bovine biology.organism_classification N-Acetylneuraminic Acid Peptide Fragments Wheat germ agglutinin Sialic acid Carbohydrate Sequence Pertussis Toxin chemistry Selectins Sialic Acids Endothelium Vascular alpha-Fetoproteins Glycoconjugates N-Acetylneuraminic acid Selectin |
| Zdroj: | Glycobiology. 5:427-433 |
| ISSN: | 1460-2423 0959-6658 |
| Popis: | Pertussis toxin, a virulence factor produced by the organism Bordetella pertussis, has been shown to have functional similarities with selectins and to bind to similar sialic acid-containing oligosaccharides structures. Previously, we demonstrated that the amino-terminal region of the S2 subunit of pertussis toxin contained a short six amino acid sequence (SPYGRC) which displayed reasonable homology to a sequence that constitutes a portion of the sialic acid binding site in wheat germ agglutinin. Synthetic peptides containing this hexapeptide motif had the ability to bind to sialic acid-containing glycoconjugates including the putative oligosaccharide receptors (sialyl Lewis X and sialyl Lewis A) for selectins. Control peptides containing randomized sequences were inactive at inhibiting binding, indicating that the hexapeptide motif is important for interacting with sialic acid. Since pertussis toxin-derived peptides demonstrated the ability to interact with selectin receptors, we speculated that they should antagonize selectin-mediated inflammatory activity. To test this hypothesis, we evaluated the peptides for the ability to reduce neutrophil binding to activated endothelial cells as well as the anti-inflammatory activity in the mouse footpad swelling assay. Both S2 peptides were active at reducing neutrophil binding and footpad swelling, while the randomized control peptides were inactive. |
| Databáze: | OpenAIRE |
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