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

ABSTRACT: 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.

SUBMITTER: Liu F

PROVIDER: S-EPMC2863121 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature

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

Liu Fa F Hakami Ramin Mollaaghababa RM Dyas Beverly B Bahta Medhanit M Lountos George T GT Waugh David S DS Ulrich Robert G RG Burke Terrence R TR

Bioorganic & medicinal chemistry letters 20100315 9

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. ...[more]

PMID: 20350805

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