H-Lys-Arg-Asn-Lys-Asn-Asn-OH is the minimal active structure of oxyntomodulin

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