Discovery of novel inhibitor of human leukocyte common antigen-related phosphatase

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• 作者：Xiaoning Yang ; Jingya Li ; Yueyang Zhou ; Qiang Shen ; Jiwu Chen and Jia Li
• 关键词：LAR ; Protein tyrosine phosphatase ; High-throughput screening ; Competitive ; Inhibitor ; meD peptide
• 刊名：Biochimica et Biophysica Acta (BBA)/General Subjects
• 出版年：2005
• 期刊代码：16_03044165
• 类别：bio
• 出版时间：2005
• 卷：1726
• 期：1
• 页码：34-41
• 文件大小：229 K

摘要

Human leukocyte common antigen-related phosphatase (LAR) may play a role in type 2 diabetes and cancer, and in the development of the nervous system, and it may be an attractive target for the treatment of diabetes and cancer. We identified eight hits from the random screening of LAR D1 with a high-throughput screening assay. Further validation of the eight hits showed that the meD insertion was associated with inhibition of LAR D1D2 and LAR D1Q. These data suggest that the inserted meD peptide influences the interaction of the enzyme and inhibitor, which is consistent with the kinetic catalysis constants of the substrate pNPP. Our data showed that Hit 1, the first published novel inhibitor of LAR, is a competitive inhibitor with a K_i of 330 nM that displays obvious selectivity for LAR and mouse PTPσ, but not for other protein tyrosine phosphatases.