Conformation-activity relationship in hexapeptides related to substance P.
Two hexapeptides related to the undecapeptide substance P (SP) Glu-Phe-Phe-Gly-Leu-Met-NH2 and Glu-Phe-Phe-Pro-Leu-Met-NH2, have been synthesized and their selectivity for the SP receptors studied. Conformational analyses of both peptides have been carried out using a molecular modeling program. Activity appears to be related to the adoption of a U-shape conformation since the Pro9 containing peptide in which this folding is favoured is much more active than the hexapeptide containing Gly9. Moreover, such a substitution induces a significant selectivity for the SP-P receptor compared to the SP-E receptor.
Elguero
J
J
Instituto de Quimica Médica Consejo Superior de Investigaciones Cientificas, Madrid, Spain.
García-Antón
J M
JM
Goya
P
P
Haro
I
I
Martínez
A
A
Reig
F
F
D000818:Animals; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008968:Molecular Conformation; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D013373:Substance P / Q000031:analogs & derivatives* / Q000494:pharmacology; D014649:Vas Deferens / Q000187:drug effects
D009842:Oligopeptides; D013373:Substance P