Rational design of a nonpeptide general chemical scaffold for reversible inhibition of PDZ domain interactions
Rational design of a nonpeptide general chemical scaffold for reversible inhibition of PDZ domain interactions
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DOI：
10.1016/j.bmcl.2006.10.006
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发表时间：
2007-01-15
影响因子：
2.7
通讯作者：
Guy, R. Kiplin
中科院分区：
文献类型：
--
作者：
Fujii, Naoaki;Haresco, Jose J.;Guy, R. Kiplin
新型小分子被设计为特异性靶向PDZ结构域的配体结合口袋。迭代的分子对接和建模允许设计吲哚支架10a作为配体结合的可逆抑制剂。10 α支架抑制MAGI-3和PTEN之间的相互作用，并显示出与NHERF-1功能抑制一致的细胞活性。(c)2006爱思唯尔有限公司保留所有权利。
Novel small molecules were designed to specifically target the ligand-binding pocket of a PDZ domain. Iterative molecular docking and modeling allowed the design of an indole scaffold 10a as a reversible inhibitor of ligand binding. The 10a scaffold inhibited the interaction between MAGI-3 and PTEN and showed cellular activities that are consistent with the inhibition of NHERF-1 function. (c) 2006 Elsevier Ltd. All rights reserved.