A rapid oxime linker-based library approach to identification of bivalent inhibitors of the Yersinia pestis protein-tyrosine phosphatase, YopH

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:20

Article

Liu, Fa¹  Hakami, Ramin Mollaaghababa^2,3  Dyas, Beverly³  Bahta, Medhanit¹  Lountos, George T.⁴  Waugh, David S.⁴  Ulrich, Robert G.³  Burke, Terrence R., Jr.¹ 

[1] NCI, Biol Chem Lab, Mol Discovery Program, Ctr Canc Res,NIH, Frederick, MD 21702 USA

[2] Oak Ridge Associated Univ, Fac Res Participat Program, Belcamp, MD 21017 USA

[3] USA, Med Res Inst Infect Dis, Lab Mol Immunol, Frederick, MD 21702 USA

[4] NCI, Macromol Crystallog Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA

关键词: Protein-tyrosine phosphatase;    Yersinia pestis;    YopH;    Inhibitor;   

DOI  :  10.1016/j.bmcl.2010.03.058

来源: Elsevier

【 摘 要 】

A bivalent tethered approach toward YopH inhibitor development is presented that joins aldehydes with mixtures of bis-aminooxy-containing linkers using oxime coupling. The methodology is characterized by its facility and ease of use and its ability to rapidly identify low micromolar affinity inhibitors. The generality of the approach may potentially make it amenable to the development of bivalent inhibitors directed against other phosphatases. Published by Elsevier Ltd.

【 授权许可】

Free