Design and Synthesis of Novel Tetra-Peptide Motilin Agonists Original Research Article

A series of novel tetra-peptide motilin agonists, having the general structure H-Phe-Val-X-Ile-NH2, were designed, on the basis of structure–activity relationship studies of motilin. Peptides, in which X is a side chain substituted tryptophan residue, have agonistic activity. H-Phe-Val-Trp(2′-CH2CH2OH)-Ile-NH2 (), H-Phe-Val-Trp(2′-SCH3)-Ile-NH2 (8), and H-Phe-Val-Trp(2′-SCH2CH2CH3)-Ile-NH2 (9), showed an EC50 for contractile activity in the rabbit smooth muscle of 14.1±3.2, 12.9±4.1, and 4.6±1.6 μM, respectively. Interaction of the tryptophan aliphatic side chain with motilin receptor appears to influence the signal transduction via motilin receptor.