Interleukin-8 antagonists generated by N-terminal modification.

摘要: We have previously shown that the residues Glu4-Leu5-Arg6 (ELR) preceding first cysteine at N terminus of 72-residue form interleukin-8 (IL-8) are essential for receptor binding and neutrophil activation (Clark-Lewis, I., Schumacher, C., Baggiolini, M., Moser, B. (1991) J. Biol. Chem. 266, 23128-23134). now synthesized a series analogs IL-8(4-72), truncated IL-8 with N-terminal sequence ELRC, as potential antagonists. Among 26 deletions or amino acid replacements in ELR region several inhibited function. The most potent were IL-8(6-72), Arg6 terminus, IL-8,AAR(7-72) Ala4-Ala5 instead Glu4-Leu5. They binding, exocytosis (IC50 0.3 microM), well chemotaxis respiratory burst. Inhibition was restricted to responses elicited by IL-8, GRO alpha, NAP-2, no effect observed when unrelated agonists fMet-Leu-Phe C5a used stimuli. These results demonstrate selective antagonists prevent attenuate action its related chemotactic cytokines obtained modification terminus.