Development of rationally designed DNA N6 adenine methyltransferase inhibitors

被引：10

作者：

Hobley, Gerard ^{[1
]}

McKelvie, Jennifer C. ^{[1
]}

Harmer, Jenny E. ^{[1
]}

Howe, Jason ^{[1
]}

Oyston, Petra C. F. ^{[2
]}

Roach, Peter L. ^{[1
]}

机构：

[1] Univ Southampton, Sch Chem, Southampton SO17 1BJ, Hants, England

[2] DSTL, Salisbury SP4 0JQ, Wilts, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 09期

基金：

英国工程与自然科学研究理事会;

关键词：

DNA methyltransferases; Inhibitors; S-Adenosylmethionine; Methylation; Epigenetics; Antibacterial; ADENOSYL-L-HOMOCYSTEINE; BISUBSTRATE INHIBITORS; POTENTIAL INHIBITORS; STRUCTURAL REQUIREMENTS; MULTISUBSTRATE ADDUCTS; YERSINIA-PESTIS; L-METHIONINE; METHYLATION; ANALOGS; ACID;

D O I：

10.1016/j.bmcl.2012.03.072

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of bisubstrate inhibitors for DNA N6 adenine methyltransferase (Dam) have been synthesized by linking an amine analogue of S-adenosylmethionine to an aryl moiety designed to probe the binding pocket of the DNA adenine base. An initial structure-activity relationship study has identified substituents that increase inhibitor potency to the similar to 10 mu M range and improve selectivity against the human cytosine methyltransferase Dnmt1. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：3079 / 3082

页数：4

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