当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Synthesis and dopamine receptor modulating activity of novel peptidomimetics of L-prolyl-L-leucyl-glycinamide featuring alpha,alpha-disubstituted amino acids.

Synthesis and dopamine receptor modulating activity of novel peptidomimetics of L-prolyl-L-leucyl-glycinamide featuring alpha,alpha-disubstituted amino acids.

Abstract：

:In the present study, L-prolyl-L-leucyl-glycinamide (1) peptidomimetics 3a-3d and 4a-4d were synthesized utilizing alpha, alpha-disubstituted amino acids. These analogues were designed to explore the conformational effects of constraints at the phi3 and psi3 torsion angles. Constrained conformations were verified by the use of X-ray crystallography and circular dichroism. The effects of Pro-Leu-Gly-NH2 analogues 3a-3d and 4a-4d on enhancing rotational behavior induced by apomorphine in the 6-hydroxydopamine-lesioned animal models of Parkinson's disease were studied. The ability of these peptidomimetics to increase the binding of agonist N-propylnorapomorphine (NPA) to the dopamine D2 receptor was also examined. Extended analogue Pro-Leu-Deg-NH2 was the most active compound of this series. It was 10 times more potent and almost 2 times more effective than 1 in increasing apomorphine-induced rotations (56 +/- 15% at 1.0 mg/kg ip) and in enhancing [3H]NPA specific binding (40%).

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Evans MC,Pradhan A,Venkatraman S,Ojala WH,Gleason WB,Mishra RK,Johnson RL

doi

10.1021/jm980656r

keywords:

subject

Has Abstract

pub_date

1999-04-22 00:00:00

pages

1441-7

issue

8

eissn

0022-2623

issn

1520-4804

pii

jm980656r

journal_volume

42

pub_type

杂志文章

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