Theoretical Study on the Mechanisms of Action of Sulfurand Nitrogen-containing Amino Acid Residues with Monofunctional Guanine Adduct Formed by Antitumor Drugs trans-[PtCl2（Am）（isopropylamine）] （Am = Isopropylamine,Dimethylamine and Propylamine） and Their cis Isomers

The mechanisms of action on monofunctional guanine adducts of analogues of transplatin with aliphatic amine ligands,such as trans-[Pt（Am）（isopropylamine）（G）（H2O）] where Am represents dimethylamine,propylamine or isopropylamine and their cis isomers reacting with sulfur- and nitrogen-containing amino acid residues,were explored. Histidine and lysine residues are chosen as the model ligands of nitrogen-containing amino acid residues of proteins; meanwhile,methionine and cysteine residues are chosen as the model ligands of sulfur-containing amino acid residues of proteins. A dominating preference for sulfur-containing ligand over nitrogen-containing ligand is established. The calculated smallest activation barrier for sulfur-containing ligand is 9.9,and 21.1 kcal/mol for nitrogen-containing ligand in aqueous solution,and both of them have trans configurations. The difference in activation energy is 11.2 kcal/mol,indicating the platination of sulfur-containing amino acid residues is faster by seven to eight orders of magnitude than that of nitrogen-containing amino acid residues.

Theoretical Study on the Mechanisms of Action of Sulfur and Nitrogen-containing Amino Acid Residues with Mono functional Guanine Adduct Formed by Antitumor Drugs trans-[PtCl_2(Am)(isopropylamine)] (Am = Isopropylamine, Dimethylamine and Propylamine) and Their cis Isomers

The mechanisms of action on monofunctional guanine adducts of analogues of transplatin with aliphatic amine ligands, such as trans-[Pt(Am)(isopropylamine)(G)(H_2O)] where Am represents dimethylamine, propylamine or isopropylamine and their cis isomers reacting with sulfur- and nitrogen-containing amino acid residues, were explored. Histidine and lysine residues are chosen as the model ligands of nitrogen-containing amino acid residues of proteins; meanwhile, methionine and cysteine residues are chosen as the model ligands of sulfur-containing amino acid residues of proteins. A dominating preference for sulfur-containing ligand over nitrogen-containing ligand is established. The calculated smallest activation barrier for sulfur-containing ligand is 9.9, and 21.1 kcal/mol for nitrogen-containing ligand in aqueous solution, and both of them have trans configurations. The difference in activation energy is 11.2 kcal/mol, indicating the platination of sulfur-containing amino acid residues is faster by seven to eight orders of magnitude than that of nitrogen-containing amino acid residues.