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Allosteric modulation of the dopamine receptor by conformationally constrained type VI beta-turn peptidomimetics of Pro-Leu-Gly-NH2.

ABSTRACT: A peptidomimetic of Pro-Leu-Pro-NH2, 7, possessing an indolizidinone type VI beta-turn mimic was synthesized via improved high-yielding protocols for the preparation and Cbz protection of alpha-allylproline. Bicyclic peptidomimetic 7 and spirobicylic peptidomimetic 8 enhanced the binding of [3H] N-propylnorapomorphine to dopamine receptors indicating that a type VI beta-turn is a possible bioactive conformation of the homochiral Pro-Leu-Pro-NH2 and Pro-Pro-Pro-NH 2 analogues of Pro-Leu-Gly-NH2 at the dopamine receptor allosteric regulatory site.

SUBMITTER: Vartak AP

PROVIDER: S-EPMC2529021 | biostudies-literature | 2007 Dec

REPOSITORIES: biostudies-literature

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Allosteric modulation of the dopamine receptor by conformationally constrained type VI beta-turn peptidomimetics of Pro-Leu-Gly-NH2.

Vartak Ashish P AP Skoblenick Kevin K Thomas Nancy N Mishra Ram K RK Johnson Rodney L RL

Journal of medicinal chemistry 20071201 26

A peptidomimetic of Pro-Leu-Pro-NH2, 7, possessing an indolizidinone type VI beta-turn mimic was synthesized via improved high-yielding protocols for the preparation and Cbz protection of alpha-allylproline. Bicyclic peptidomimetic 7 and spirobicylic peptidomimetic 8 enhanced the binding of [3H] N-propylnorapomorphine to dopamine receptors indicating that a type VI beta-turn is a possible bioactive conformation of the homochiral Pro-Leu-Pro-NH2 and Pro-Pro-Pro-NH 2 analogues of Pro-Leu-Gly-NH2 a ...[more]

PMID: 18052024

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