Investigation of Interactions between an Organoruthenium Anticancer Complex and a Mimic of PTP1B Using LC/MS

Protein tyrosine phosphatase 1B(PTP 1B) which contains a catalytic cysteine plays important role in the negative regulating of insulin signaling, and it has been investigated as a therapeutic target in type II diabetes and obesity. In the present work, the reactions of ruthenium anticancer complex(ŋ⁶-cymene)Ru(en)ClPF₆ with the model compound(2-mercaptobenzanilide) were studied under physiologically relevant conditions. Then we treated the mono- and di-ruthenium product with GSH and H₂O₂ to mimic the inactivation and activation of PTP1B whilst (ŋ⁶-cym)Ru(en)ClPF₆ binds to the active site of PTP1B. HPLC-ESI-MS time courses suggest that organometallic ruthenium complexes may inhibit the enzymatic activity of PTP1B by coordinating to the thiol in the active site, which may have important biological and pharmacologic significances in the treatment of diabetes and obesity.