期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 26, 期 18, 页码 4542-4547出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2015.10.015
关键词
UBA5; UFM1; Noncompetitive inhibition; E1 activating enzyme; Ubiquitin-like protein
资金
- Canadian Cancer Society Research Innovation Grant [701486]
- National Institutes of Health [R01 GM081776]
- Natural Sciences and Engineering Research Council of Canada
Protein conjugation with ubiquitin and ubiquitin-like small molecules, such as UFM1, is important for promoting cancer cell survival and proliferation. Herein, the development of the first selective micromolar inhibitor of the UBA5 E1 enzyme that initiates UFM1 protein conjugation is described. This organometallic inhibitor incorporates adenosine and zinc(II) cyclen within its core scaffold and inhibits UBA5 noncompetitively and selectively over other E1 enzymes and a panel of human kinases. Furthermore, this compound selectively impedes the cellular proliferation (above 50 mu M) of cancer cells containing higher levels of UBA5. This inhibitor may be used to further probe the intracellular role of the UFM1 pathway in disease progression. (C) 2015 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据