Utilization of sialic acid-binding synthetic peptide sequences derived from pertussis toxin as novel anti-inflammatory agents

Pertussis toxin, a virulence factor produced by the organismBordetella pertussis, has been shown to have functional similaritieswith selectins and to bind to similar sialic acid-containingoligosaccharides structures. Previously, we demonstrated thatthe amino-terminal region of the S2 subunit of pertussis toxincontained a short six amino acid sequence (SPYGRC) which displayedreasonable homology to a sequence that constitutes a portionof the sialic acid binding site in wheat germ agglutinin. Syntheticpeptides containing this hexapeptide motif had the ability tobind to sialic acid-containing glycoconjugates including theputative oligosaccharide receptors (sialyl Lewis X and sialylLewis A) for selectins. Control peptides containing randomizedsequences were inactive at inhibiting binding, indicating thatthe hexapeptide motif is important for interacting with sialicacid. Since pertussis toxin-derived peptides demonstrated theability to interact with selectin receptors, we speculated thatthey should antagonize selectin-mediated inflammatory activity.To test this hypothesis, we evaluated the peptides for the abilityto reduce neutrophil binding to activated endothelial cellsas well as the anti-inflammatory activity in the mouse footpadswelling assay. Both S2 peptides were active at reducing neutrophilbinding and footpad swelling, while the randomized control peptideswere inactive. anti-inflammatory agents peptides pertussis toxin