Probing binding requirements of NAD kinase with modified substrate (NAD) analogues

被引：27

作者：

Bonnac, Laurent

Chen, Liqiang

Pathak, Rashmi

Gao, Guangyao

Ming, Qian

Bennett, Eric

Felczak, Krzysztof

Kullberg, Martin

Patterson, Steven E.

Mazzola, Francesca

Magni, Giulio

Pankiewicz, Krzysztof W. ^{[1
]}

机构：

[1] Univ Minnesota, Ctr Drug Design, Minneapolis, MN 55455 USA

[2] Univ Politecn Marche, Inst Biotecnol Biochim, I-60131 Ancona, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 06期

关键词：

NAD kinase; M; tuberculosis; benzamide adenine dinucleotide (BAD); NAD analogues;

D O I：

10.1016/j.bmcl.2007.01.012

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Synthesis of novel NAD(+) analogues that cannot be phosphorylated by NAD kinase is reported. In these analogues the C2' hydroxyl group of the adenosine moiety was replaced by fluorine in the ribo or arabino configuration (1 and 2, respectively) or was inverted into arabino configuration to give compound 3. Compounds 1 and 2 showed inhibition of human NAD kinase, whereas analogue 3 inhibited both the human and Mycobacterium tuberculosis NAD kinase. An uncharged benzamide adenine dinucleotide (BAD) was found to be the most potent competitive inhibitor (K-i = 90 mu M) of the human enzyme reported so far. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：1512 / 1515

页数：4

共 28 条

[1] EFFECT OF ALKYLATION ON SUBSTRATE-BINDING AND EFFECTOR-BINDING SITES IN PIGEON LIVER NAD KINASE [J].