Conformation-activity relationship in hexapeptides related to substance P
Elguero, J.; García-Antón, J.M.; Goya, P.; Haro, I.; Martínez, A.; Reig, F.
Arzneimittel-Forschung 39(8): 835-838
1989
ISSN/ISBN: 0004-4172 PMID: 2479388 Document Number: 339138
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.