淋巴样酪氨酸磷酸酶的抑制作用：锌（II）离子和螯合配体片段对酶活性的影响。
Inhibition of the lymphoid tyrosine phosphatase: the effect of zinc(II) ions and chelating ligand fragments on enzymatic activity.
作者信息
Thorson Megan K, Puerta David T, Cohen Seth M, Barrios Amy M
机构信息
Department of Medicinal Chemistry, University of Utah, 30 South 2000 East, Salt Lake City, UT 84112, USA.
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.
出版信息
Bioorg Med Chem Lett. 2014 Aug 15;24(16):4019-22. doi: 10.1016/j.bmcl.2014.06.016. Epub 2014 Jun 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 value of 2.52±0.06 μM 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.
对一个由96个成员组成的螯合剂片段文库（CFL-1.1）进行了筛选，以鉴定在不存在和存在乙酸锌的情况下淋巴细胞酪氨酸磷酸酶的抑制剂。鉴定出了在锌存在下更有效地抑制LYP活性的片段、在存在抑制浓度的锌时能恢复LYP活性的片段以及与锌浓度无关而抑制LYP活性的片段。其中，1,2-二羟基萘是最有效的抑制剂，孵育2小时后的IC50值为2.52±0.06μM。1,2-二羟基萘对LYP的抑制作用与1,2-萘醌的抑制作用非常相似（IC50 = 1.10±0.03μM），表明氧化的醌类物质可能是活性抑制剂。这种抑制作用是时间依赖性的，与该酶的共价修饰一致。
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