STRUCTURE-FUNCTION STUDIES IN A SERIES OF CARBOXYL-TERMINAL OCTAPEPTIDE ANALOGS OF ANAPHYLATOXIN-C5A

The synthesis and structure-activity relationships of C-terminal octapeptide analogues of anaphylatoxin C5a have been studied. The introduction of hydrophobic amino acids into the N-acetylated native octapeptide (N-Ac-His-Lys-Asp-Met-Gln-Leu-Gly-Arg-OH) (1) has led to an analogue with 100 times more activity than the native octapeptide in inhibiting the binding of I-125-labeled anaphylatoxin C5a to human neutrophil membrane receptors. The observed apparent binding K(l)'s for the compounds (8-10) are in the range of 1-3-mu-M, and they possess nearly full agonist activity, despite the fact that these analogues are one-eight or -ninth the size of the natural ligand anaphylatoxin C5a.