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.
D000595:Amino Acid Sequence; D000818:Animals; D001681:Biological Assay; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D007202:Indicators and Reagents; D013329:Structure-Activity Relationship; D013373:Substance P / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology
D007202:Indicators and Reagents; D013373:Substance P