Synthesis of partially modified retro-inverso substance P analogues and their biological activity

Partial retro-inverso modification of a single peptide bond was applied to pGlu-Phe-Phe-Gly-Leu-Met-NH2 (I), a C-terminal hexapeptide analogue of the neuropeptide substance P. Two analogues with reversed peptide bonds, between the pGlu-Phe and Phe-Gly residues, were prepared, purified and characterized. The analogue gpGlu-(RS)-mPhe-Phe-Gly-Leu-Met-NH2 (II) was devoid of either agonistic or antagonistic activity. The second pseudopeptide analogue, i.e., pGlu-Phe-gPhe-mGly-Leu-Met-NH2 (III), was found to be a full agonist with 22% of the potency of I in the guinea pig ileum assay.