DESIGN AND EVALUATION OF SMALL PEPTIDES MAPPING THE EXPOSED SURFACE OF IL-8

In an effort to determine which regions of IL-8 are involved in intera ctions with its receptors, eight peptides were designed to correspond to distinct exposed regions of the IL-8 monomer, using the proton NMR- derived structure of the dimer as a basis. The peptides were evaluated singularly, and as equimolar mixtures of two to six peptides, in an I L-8 receptor binding assay and found to have no binding interaction wi th either alpha or beta IL-8 receptor as single peptides or mixtures o f two peptides. In contrast, one of these peptides having the sequence AVLPRSAKEL, which corresponds to the N-terminal 10 amino acid residue s of the 77 amino acid form of IL-8, exhibited potent chemotactic acti vity in human neutrophils. These results indicate that there is no con tiguous ligand that can be designed based on the NMR and X-ray determi ned structure of IL-8 and that there may be multiple receptors respons ible for neutrophil activation and chemotaxis.