Inhibition of the lymphoid tyrosine phosphatase: The effect of zinc(II) ions and chelating ligand fragments on enzymatic activity |
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| Institution: | 1. Department of Medicinal Chemistry, University of Utah, 30 South 2000 East, Salt Lake City, UT 84112, USA;2. Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA;1. School of Textiles, Tianjin Polytechnic University, Tianjin 300387, PR China;2. Intelligent Textile and Energy–saving Products Innovation Platform, Tianjin Polytechnic University, Tianjin 300387, PR China;3. Department of Chemistry, Taiyuan Normal University, Jinzhong 030619, PR China;4. Department of Chemistry, Hebei Normal University of Science & Technology, Qinhuangdao 066004, PR China;1. School of Chemistry and Environmental Engineering, Yancheng Teachers University, Yancheng 224002, PR China;2. Department of Chemistry, Taiyuan Normal University, Jinzhong 030619, PR China;1. Fakultät für Mathematik, Universität Bielefeld, Postfach 10 01 31, 33501 Bielefeld, Germany;2. The School of Computer Sciences, The Academic College of Tel-Aviv–Yaffo, 2 Rabenu Yeruham St., Tel-Aviv 61083, Israel;1. Department of Chemistry, Taiyuan Normal University, Jinzhong 030619, PR China;2. Key Laboratory of Advanced Energy Materials Chemistry (Ministry of Education), Nankai University, Tianjin 300071, PR China;3. Department of Biology, Taiyuan Normal University, Jinzhong 030619, PR China;4. Petro China Pipeline Company, Langfang 065000, PR China;1. School of Chemistry and Environmental Engineering, Yancheng Teachers University, Yancheng 224002, PR China;2. Department of Chemistry, Taiyuan Normal University, Jinzhong 030619, PR China;3. Key Laboratory of Advanced Energy Materials Chemistry (Ministry of Education), Nankai University, Tianjin 300071, PR China;4. Petro China Pipeline Company, Langfang 065000, PR China;1. Martin-Luther Universität Halle-Wittenberg, Bereich Organische Chemie, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany;2. Chiroblock GmbH, Andresenstr. 1a, D-06766 Bitterfeld-Wolfen, Germany |
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| 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 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. |
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| Keywords: | Chelator fragment library Protein tyrosine phosphatase Enzyme inhibitors |
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