UTILIZATION OF SIALIC ACID-BINDING SYNTHETIC PEPTIDE SEQUENCES DERIVED FROM PERTUSSIS TOXIN AS NOVEL ANTIINFLAMMATORY AGENTS

Pertussis toxin, a virulence factor produced by the organism Bordetell a pertussis, has been shown to have functional similarities,vith selec tins and to bind to similar sialic acid-containing oligosaccharides st ructures. Previously, we demonstrated that the amino-terminal region o f the S2 subunit of pertussis toxin contained a short six amino acid s equence (SPYGRC) which displayed reasonable homology to a sequence tha t constitutes a portion of the sialic acid binding site in wheat germ agglutinin. Synthetic peptides containing this hexapeptide motif had t he ability to bind to sialic acid-containing glycoconjugates including the putative oligosaccharide receptors (sialyl Lewis X and sialyl Lew is A) for selectins. Control peptides containing randomized sequences were inactive at inhibiting binding, indicating that the hexapeptide m otif is important for interacting with sialic acid, Since pertussis to xin-derived peptides demonstrated the ability to interact with selecti n receptors, we speculated that they should antagonize selectin-mediat ed inflammatory activity, To test this hypothesis, we evaluated the pe ptides for the ability to reduce neutrophil binding to activated endot helial cells as well as the anti-inflammatory activity in the mouse fo otpad swelling assay. Both S2 peptides were active at reducing neutrop hil binding and footpad swelling, while the randomized control peptide s were inactive.