Synthesis and in vitro evaluation of [Leu 13]porcine motilin fragments

Abstract

Several peptide fragments representing N- terminal , C- terminal , and internal sequences of [Leu 13]porcine motilin ([Leu 13]pMOT) were synthesized using Fmoc solid phase methodology. Peptides were assayed for motilin receptor binding activity in a rabbit antrum smooth muscle preparation and for stimulation of contractile activity in segments of rabbit duodenum. In vitro activity was directly correlated with motilin receptor binding affinity for all [Leu 13]pMOT fragments examined. N- Terminal fragments of just over half the length of the native peptide are nearly equipotent as full-length motilin. These results suggest that the N- terminal segment, together with residues from the mid-portion of the molecule, constitutes the bioactive portion of pMOT. The C- terminal segment, in contrast, contributes little to receptor binding affinity or in vitro activity.