Dopamine Receptor Modulation by a Highly Rigid Spiro Bicyclic Peptidomimetic of Pro-Leu-Gly-NH2

Michael J. Genin, Ram K. Mishra, Rodney L. Johnson

Research output: Contribution to journalComment/debatepeer-review

51 Scopus citations

Abstract

A peptidomimetic analogue of Pro-Leu-Gly-NH2 (PLG), compound 3, has been synthesized that contains a highly constrained spiro bicyclic type-II β-turn mimic. Peptidomimetic 3 enhanced the binding of the dopamine receptor agonist ADTN to dopamine receptors by 40% at 10−6 M. At this same concentration PLG enhanced the binding of ADTN by 26%. Like PLG, 3 exhibited a bell-shaped dose-response curve with the maximum effect occurring at a concentration of 10−6 M. Because of the highly rigid nature of the spiro bicyclic type-II β-turn constraint found in 3, these results lend strong support for the hypothesis that the biologically active conformation of PLG is a type-II β-turn.

Original languageEnglish (US)
Pages (from-to)3481-3483
Number of pages3
JournalJournal of medicinal chemistry
Volume36
Issue number22
DOIs
StatePublished - 1993

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