Identification, Synthesis and Biological Activity of Galloyl Inhibitors of Human Low Molecular Weight Protein Tyrosine Phosphatase
Chemistry | Physical Sciences and Mathematics
Edward J. McIntee, Chemistry; Henry V. Jakubowski, Chemistry
Low Molecular Weight Protein Tyrosine Phosphatase (LMW-PTP) isoform 2 (IF2) has been found to be over expressed in many forms of aggressive cancer and has become a target for inhibition. Competitive inhibition of LMW-PTP IF2 by known inhibitor pyridoxal-5'-phosphate (PLP) shows a strong inhibition constant (Ki = 7.6 μM at pH 5.0); however, PLP is a cofactor for many other enzymes. In silico screening and in vitro testing identified NSC107022 (Ki = 10.8 ±1.0) from the National Cancer Institute's Diversity Set II as a lead compound for optimization as a LMW-PTP IF2 inhibitor. Utilizing NSC107022's galloyl group, compound libraries of aromatic alcohols and amines were connected (ester and amide linkages, respectively) and screened in silico. Twelve compounds, eight esters and four amides yielding top docking scores (most negative) were selected for synthesis and in vitro screening.
Klinker, Samuel T., "Identification, Synthesis and Biological Activity of Galloyl Inhibitors of Human Low Molecular Weight Protein Tyrosine Phosphatase" (2015). Honors Theses, 1963-2015. 87.