Reaction Rates of Amino Acids with Derivatives of the Anticancer Drug Cisplatin

We are studying reactions of cisplatin derivatives, which differ in both size and shape, with various amino acids. When reaction with DNA occurs, apoptosis is observed, ideally leading to termination of the cancer. Due to the affinity of cisplatin for sulfur-containing amino acids, reaction with proteins may occur prior to access to the DNA, producing a large array of products, which could potentially be toxic to the human body. Both the size and shape of the platinum complexes often affect the reactions with protein targets more so than with DNA targets. By performing reactions of specific amino acids targets with our cisplatin derivatives, we attempt to understand the factors that influence the targeting of these specific amino acids. In this study, cisplatin derivatives have been reacted with the amino acids histidine, cysteine, and methionine, and the reactions have been monitored by NMR spectroscopy, and rate constants calculated using DYNAFIT. It has been seen that adding bulk to the ligands of our platinum compounds has little to no effect on the reaction with histidine compared with methionine and cysteine targets. Thus, sufficient bulk may increase the relative number of histidine adducts compared with methionine or cysteine adducts, consequently decreasing the toxic side effects experienced by users of the drug