有哪些信誉好的足球投注网站high throughput screens yield small molecule inhibitors of leishmania crk3cyc6 cyclin-dependent kinase高吞吐量屏幕产生的小分子抑制剂利什曼虫crk3cyc6细胞周期蛋白依赖性激酶.pdfVIP
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high throughput screens yield small molecule inhibitors of leishmania crk3cyc6 cyclin-dependent kinase高吞吐量屏幕产生的小分子抑制剂利什曼虫crk3cyc6细胞周期蛋白依赖性激酶
High Throughput Screens Yield Small Molecule Inhibitors of Leishmania CRK3:CYC6 Cyclin-Dependent Kinase 1 2 3 4 1 Roderick G. Walker , Graeme Thomson , Kirk Malone , Matthew W. Nowicki , Elaine Brown , David G. 2 3 4 5 1 Blake , Nicholas J. Turner , Malcolm D. Walkinshaw , Karen M. Grant , Jeremy C. Mottram * 1 Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom, 2 Cyclacel Ltd., Dundee, Dundee, United Kingdom, 3 Manchester Interdisciplinary Biocentre, University of Manchester, Manchester, United Kingdom, 4 Institute of Structural and Molecular Biology, The University of Edinburgh, Edinburgh, United Kingdom, 5 School of Health Medicine, Division of Medicine, Lancaster University, Lancaster, United Kingdom Abstract Background: Leishmania species are parasitic protozoa that have a tightly controlled cell cycle, regulated by cyclin-dependent kinases (CDKs). Cdc2-related kinase 3 (CRK3), an essential CDK in Leishmania and functional orthologue of human CDK1, can form an active protein kinase complex with Leishmania cyclins CYCA and CYC6. Here we describe the identification and synthesis of specific small molecule inhibitors of bacterially expressed Leishmania CRK3:CYC6 using a high throughput screening assay and iterative chemistry. We also describe the biological activity of the molecules against Leishmania parasites. Methodology/Principal Findings: In order to obtain an active Leishmania CRK3:CYC6 protein kinase complex,
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