H-LYS-ARG-ASN-LYS-ASN-ASN-OH IS THE MINIMAL ACTIVE STRUCTURE OF OXYNTOMODULIN

Oxyntomodulin inhibits gastric acid secretion via its C-terminal octap eptide. Its minimal active structure was delineated by testing, on his tamine-stimulated gastric acid secretion in the conscious rat, the inh ibitory effect of octapeptide analogues, shortened either or both on t heir N- or C-terminus. The octapeptide may be simplified by deleting t he two C-terminal amino acids while keeping its efficacy and the slope of the dose-response curve. Suppressing the first N-terminal amino ac id dramatically decreased the activity. The nonprotected peptides are metabolized by aminopeptidases and endopeptidases. The increased poten cy of the N-acetylated forms is related, at least in part, with their protection against aminopeptidases.