Conformationally restricted cyclic analogues of substance P: insight into the receptor binding process |
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Authors: | P S Darman G C Landis J R Smits L D Hirning K Gulya H I Yamamura T F Burks V J Hruby |
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Affiliation: | 1. Department of Chemistryl, University of Arizona, Tucson, Arizona 85721, USA;2. Department of Pharmacology, University of Arizona, Tucson, Arizona 85721, USA |
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Abstract: | Three new cyclic substance P analogues were prepared to examine the possible role of a pseudocyclic turn structure for receptor recognition. In the guinea pig isolated ileum [Cys5, Cys11]-SP5-11-NH2 and [Cys6, Cys11]-SP5-11-NH2 were inactive at concentrations up to 100 microM, while [Cys5, Cys6, Nle11]-SP was a weak agonist. The order of relative affinities on the rat brain radioreceptor assay was as follows: [Cys5, Cys6, Nle11]-SP greater than [Cys5, Cys11]-SP5-11-NH2 greater than [Cys6, Cys11]-SP5-11-NH2. We interpret these results to indicate that a pseudocyclic structure of the 5-11 sequence may not be an important factor involved in the receptor recognition of substance P. |
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Keywords: | p-MBHA p-methylbenzhydrylamineresin Nle norleucine TFA trifluoroacetic acid DMF dimethylformamide t-Boc t-butoxycarbonyl |
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