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Inhibition of the lymphoid tyrosine phosphatase: the effect of zinc(II) ions and chelating ligand fragments on enzymatic activity.

ABSTRACT: A 96-member chelator fragment library (CFL-1.1) was screened to identify inhibitors of the lymphoid tyrosine phosphatase in the absence and presence of zinc acetate. Fragments that inhibit LYP activity more potently in the presence of zinc, fragments that rescue LYP activity in the presence of inhibitory concentrations of zinc, and fragments that inhibit LYP activity independent of zinc concentration were identified. Of these, 1,2-dihydroxynaphthalene was the most potent inhibitor with an IC50 value of 2.52±0.06 ?M after 2 h of incubation. LYP inhibition by 1,2-dihydroxynaphthalene was very similar to inhibition by 1,2-naphthoquinone (IC50=1.10±0.03 µM), indicating that the oxidized quinone species is likely the active inhibitor. The inhibition was time-dependent, consistent with covalent modification of the enzyme.

SUBMITTER: Thorson MK

PROVIDER: S-EPMC4497560 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Inhibition of the lymphoid tyrosine phosphatase: the effect of zinc(II) ions and chelating ligand fragments on enzymatic activity.

Thorson Megan K MK Puerta David T DT Cohen Seth M SM Barrios Amy M AM

Bioorganic & medicinal chemistry letters 20140616 16

A 96-member chelator fragment library (CFL-1.1) was screened to identify inhibitors of the lymphoid tyrosine phosphatase in the absence and presence of zinc acetate. Fragments that inhibit LYP activity more potently in the presence of zinc, fragments that rescue LYP activity in the presence of inhibitory concentrations of zinc, and fragments that inhibit LYP activity independent of zinc concentration were identified. Of these, 1,2-dihydroxynaphthalene was the most potent inhibitor with an IC50 v ...[more]

PMID: 24997687

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