Organometallic Scaffolds as Protein Tyrosine Phosphatase 1B Inhibitor

Abstract

This thesis describes the synthesis of two novel classes of organo-ruthenium and organo-gold complexes as inhibitors of protein tyrosine phosphatases (PTPs). These organo-metallic complexes were rationally designed to be inhibitors of PTPs by attaching a non-hydrolyzable mimetic of phosphotyrosine to the ruthenium(II) and gold(I) metal centers respectively. The series of organo-ruthenium complexes have been found to inhibit protein tyrosine phosphatase 1B (PTP-1B) at low micromolar level with 7-10 fold selectivity towards PTP-1B over T-cell protein tyrosine phosphatase (TC-PTP). Molecular docking studies have also shown that the organo-ruthenium complexes bind better than the parent ligands in PTP-1B due to additional hydrophobic interactions with Phe182. These results suggest that this new class of organo-ruthenium complexes may be promising therapeutic agents to target PTP-1B. Similarly, one alkynyltriphenylphosphinegold(I) complex has been synthesized. Future work will include synthesizing a library of gold(I) complexes bearing a variety of phosphine ligands and evaluating these organo-gold(I) complexes as inhibitors of PTPs.