Synthesis and Evaluation of Novel Phosphotyrosine Mimetic-Containing Probes Targeting Protein Tyrosine Phosphatase 1B (PTP1B)
Date Issued
2012
Date
2012
Author(s)
Handoko
Abstract
Protein tyrosine phosphatase 1B (PTP1B), a member of protein tyrosine phosphatase (PTPs) enzyme family of which the primary function is to catalytically dephosphorylate phosphotyrosine residues of their respective substrates, has for a decade been known to negatively regulate the insulin signaling pathway. This led to intense research on PTP1B as a viable therapeutic target for the treatment of type 2 diabetes and obesity. However, due to high structural and sequential homology of PTP1B with T-cell protein tyrosine phosphatase (TCPTP), it is essential to find probes and inhibitors that will preferentially target PTP1B. Herein, in this thesis we described the synthesis of several phosphotyrosine mimetic-containing probes and subsequently evaluated their performance across various PTPs. Preliminary data gave encouraging results with preferential labelling towards PTP1B, prompting us to further refine our models with the assistance of computational molecular docking software. Four additional probes were then synthesized in the hope that they could exhibit higher specificity towards PTP1B.
Subjects
selective labelling
phophotyrosine mimetics
probe
molecular docking
SDGs
Type
thesis
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