title: A combinatorial strategy for the acquisition of potent and specific protein tyrosine phosphatase inhibitors.
abstract: Protein tyrosine phosphatases (PTPs), a large family of signaling enzymes, regulate many cellular processes, such as proliferation, differentiation, migration, apoptosis, and immune responses. Small molecule inhibitors against PTPs are valuable both as powerful tools to study the functions of target PTPs and as lead compounds for pharmacological development. Here, we describe a novel combinatorial library approach to target simultaneously both the active site pocket and a peripheral secondary binding site for the acquisition of potent and specific PTP inhibitors. Fluorescence tagging during combinatorial library synthesis enables fluorescence polarization-based high-throughput screening of the resulting library, leading to identification of a TC-PTP inhibitor.
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhang
authors.forename: Lan
authors.initials: L
authors.lastname: Chen
authors.forename: David S
authors.initials: DS
authors.lastname: Lawrence
authors.forename: Zhong-Yin
authors.initials: ZY
authors.lastname: Zhang
mesh_terms: D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D004791:Enzyme Inhibitors; D017027:Protein Tyrosine Phosphatases