Pascal Schmitt

N-acylated pentapeptides antagonists of substance P on guinea-pig ileum.

Summary Pentapeptides X-D,Trp-Phe-D.Trp-Leu-Y-NH2 (X = H, Boc, parachydroxyphenylacetyl, Y = Met,Leu,Nle,Phe) were tested as antagonists against Substance P and against a specific agonist of the muscular receptor of neurokinins on the guinea-pig ileum . Weak antagonist or agonist activities could be observed with the free or the Boc-protected pentapeptides whilst the acylated compounds could be compared favorably with the best antagonists already described.

Activity of the C-terminal part of substance P on guinea pig ileum and trachea preparations I. N-acylated pentapeptides SP(7–11)

Abstract Acylated pentapeptide XPhePheGlyLeuMetNH2 analogs of the substance P (7–11) sequence were synthesized by solution method and their spasmogenic activities were evaluated on guinea pig ileum (GPI) and trachea (GPT). Pentapeptide SP(7–11) had the lowest potency and its N-acylation increased its activity in both tests, with some derivatives being more active than SP itself. Results obtained on GPI suggest a close dependence of activity upon structural factors in the vicinity of the Phe7 N-terminus, whereas the activity on GPT seems more dependent upon the hydrophobicity of the analogs.

Synthesis and biological activities of neurokinin pseudopeptide analogues containing a reduced peptide bond

A series of pseudopeptides, analogues of neurokinin selective agonists, in which a peptide bond was replaced by a (CH2NH) bond were synthesized. The biological activities of these compounds were determined on selective pharmacological preparations: the dog carotid artery for NK-1, the rabbit pulmonary artery devoid of endothelium for the NK-2 and the rat portal vein for the NK-3 receptors. The results reported in this study indicate that insertion of a pseudopeptide bond in various positions of these selective agonists resulted in a great decrease in potency compared to the parent compounds. Furthermore, the selectivity of agonists is maintained by the use of a methylene amino group in position 9–10 (Sar) for the NK-1 or in position 7–8 (MePhe) for the NK-3 selective compound. The selectivity is greatly diminished for the NK-2 analogues.

N-acylated pentapeptides antagonists of substance P on guinea-pig ileum

Pentapeptides X-D.Trp-Phe-D.Trp-Leu-Y-NH2 (X = H, Boc, parahydroxyphenylacetyl, Y = Met,Leu,Nle,Phe) were tested as antagonists against Substance P and against a specific agonist of the muscular receptor of neurokinins on the guinea-pig ileum. Weak antagonist or agonist activities could be observed with the free or the Boc-protected pentapeptides whilst the acylated compounds could be compared favorably with the best antagonists already described.