Structure -: Activity relationship studies of spinorphin as a potent and selective human P2X3 receptor antagonist

被引：29

作者：

Jung, Kwan-Young

Moon, Hyoun Duk

Lee, Ga Eun

Lim, Hyun-Ho

Park, Chul-Seung

Kim, Yong-Chu ^{[1
]}

机构：

[1] Gwangju Inst Sci & Technol, Dept Life Sci, Kwangju 500712, South Korea

[2] Anygen Co Ltd, Div Drug Discovery, Kwangju 500712, South Korea

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2007年 / 50卷 / 18期

关键词：

D O I：

10.1021/jm070114m

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Spinorphin, an endogenous antinociceptive peptide (LVVYPWT), showed potent and non-competitive antagonism at the ATP-activated human P2X(3) receptor (IC50 = 8.3 pM) in a two-electrode voltage clamp assay with recombinant human P2X(3) receptors expressed in Xenopus oocytes. Single alanine substitutions from 1st to 4th amino acids and the cyclic form of LVVYPWT sustained antagonistic properties at the human P2X(3) receptors, whereas the threonine to alanine substitution resulted in an enhancing effect of the agonistic activity.

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页码：4543 / 4547

页数：5

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