REU Project 7—Reaction of platinum(II) diamine and triamine complexes with selenocysteine—Dr. Kevin Williams, Chemistry Department
Cisplatin and its analogs react with both DNA and protein tar-gets both in vitro and in vivo. Whereas reaction with DNA is thought to be responsible for the anticancer activity of cisplatin, reaction with proteins is extensive and may lead to toxicity or resistance. Methionine is one of the primary targets of platinum(II) complexes in proteins. However, we have recently found that [Pt(dien)Cl]Cl, where dien = diethylenetriamine, reacts faster with selenomethionine than with me-thionine. Thermodynamically, a slow equilibrium is reached between the methionine and selenomethionine products. Whereas selenomethionine is thought to be randomly incorporated into proteins, selenocysteine is known to be intentionally introduced into proteins and is often referred to as the "21st amino acid". We hypothesize that selenocysteine will react with platinum(II) complexes more quickly than cysteine. We will, therefore, study the reactions of selenocysteine with a variety of platinum(II) diamine and triamine complexes that we have studied previously in our laboratory. The products of reaction will be characterized by a combination of 1H, 195Pt, and possibly 77Se NMR spectroscopies as well as mass spectrometry. We will determine the rates of reaction relative to those with cysteine, methionine, and selenomethionine in order to determine whether reaction with selenocysteine could be important biologically. This research project is closely related to a larger platinum research project that has been ongoing for several years. REU students may have the opportunity to interact with WKU students who have been working on the larger ongoing project.
- Williams, K.M.; *Chapman, D.J.; *Massey, S.R.; *Haare, C. “Interaction of N-acetylmethionine with a non-C2-symmetrical platinum diamine complex”, J. Inorg. Biochem., 2005, 99, 2119-2126;
- Williams, K.M.; *Rowan, C.; *Mitchell, J. “Effect of Amine Ligand Bulk on the Interac-tion of Methionine with Platinum(II) Diamine Complexes”, Inorg. Chem., 2004, 43, 1190-1196.