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pubmed:abstractText |
Analogues of [Orn6]-SP6-11 have been synthesized in which the Met11-NH2 residue is replaced by the alpha, gamma-dimethyl, alpha, gamma-dibenzyl and alpha, gamma-di-tert-butyl esters of glutamic acid. These analogues were tested in three in vitro preparations representative of NK-1, NK-2 and NK-3 receptor types for agonist and antagonist activity. The dimethyl analogue is a selective full agonist in the NK-1 receptor type and a weak antagonist in the other two receptor types, while the dibenzyl and the di-tert-butyl analogues are potent antagonists in the NK-1 receptor type and weak antagonists in the other two receptor types. It is concluded that appropriate modification at the alpha-carboxamide and the side chain of the methionine residue of substance P may induce antagonism without using D-amino acids.
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