HIGH-AFFINITY RESPONSE-SELECTIVE C-TERMINAL ANALOGS OF C5a ANAPHYLATOXIN

摘要

High-affinity response-selective C-terminal analogs of C5a anaphylatoxin are provided. Whereas natural C5a has considerable flexibility in the C-terminal region, the analogs of the invention possess a backbone conformation which is constrained at the C-terminus to a beta -turn. The stabilized beta -turn confers a marked increase in potency of the analogs; the particular beta -turn motif further confers the capability to selectively elicit certain biological responses associated with C5a. Exemplary compounds of the invention are decapeptide analogs of the formula: A1-Ser-Phe-Lys-A2-A3-A4-A5-A6-A7, with the constrained beta -turn being localized in the region of A4-A7.