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3D PHARMACOPHORE FOA THE DESIGN OF HUMAN POLY ADENOSINE RIBONUCLEASE (PARN) INHIBITORS

机译:3D药底物是人类多聚腺苷核糖核酸酶(PARN)抑制剂的设计

摘要

The present invention relates to means and methods for the design of highly specific anti-PARN agent using our 3D pharmacophore. Using a library of previously published modified nucleoside analog substrates acting in the proximity of the scissile bond of PARN, we conducted structure - activity relationship (SAR) analysis, structural characterization and complex (receptor-ligand) based molecular dynamics simulations that led to the design of a PARN-specific pharmacophore. Our full pharmacophore consists of five pharmacophoric annotation points, which include two hydrogen donating PAPs, one hydrophobic PAP, one aromatic PAP and a hydrogen accepting PAP, in the vicinity of human poly-Adenosine ribonuclease catalytic site.
机译:本发明涉及使用我们的3D药效团设计高特异性抗PARN剂的手段和方法。使用先前发表的修饰的核苷类似物底物在PARN的易裂键附近起作用的库,我们进行了结构-活性关系(SAR)分析,结构表征和基于复杂(受体-配体)的分子动力学模拟,从而进行了设计PARN特异性药效团的制备。我们完整的药效基团由五个药效基团注释点组成,包括在人多腺苷核糖核酸酶催化位点附近的两个供氢PAP,一个疏水性PAP,一个芳香族PAP和一个氢接受PAP。

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