Study of the reactions between platinum(II) complexes and l-methionine in the presence and absence of 5′-GMP

Coordination of platinum therapeutic agents to met-rich motifs of human copper transport protein1

“…Many model studies have used stable tridentate chelates of diethylenetriamine (dien) in order to suppress ligand loss and focus exclusively on the Pt-S bonding interaction. [43][44][45][46][47][48][49] However, the potential replacement of the pendant ligands on Pt drugs will have important repercussions on the mechanism of action of Ctr1-transported Pt, since the cis-diamminePt(II) core is the active metal complex that binds to DNA to affect its cytotoxic action. Therefore we focus here exclusively on the interactions of hCtr1 peptides with the clinically important drugs themselves.…”

Interactions of the Platinum(II) Complexes with Nitrogen- and Sulfur-Bonding Bio-Molecules in Chronic Lymphocytic Leukemia

“…(Chen et al, 1998) Reaction between [Pt(dien)Cl] + complexes and Lmethionine was studied in the presence of 5'-GMP, assuming the existence of competition of this two ligands. (Lampers & Reedijk, 1990;Soldatović & Bugarčić, 2005 INO, 5'-IMP and 5'-GMP can coordinate to metal ions via N1 and N7. (Arpalahti & Lehikoinen, 1990;Arpalahti & Lippert, 1990;Caradonna & Lippard, 1988;Bose et al, 1986;Martin, 1999) Under pH = 2.5 only the N7 position of INO, 5'-IMP and 5'-GMP will be free for coordination to the central metal atom, since at this pH the N1 position is protonated.…”

“…It is expected that at neutral pH the phosphate residue on the nucleotide will also bind to the central metal atom as a result of its deprotonation. (Jacobs et al, 1992) From a comparison of the reactivity of GSH or L-methionine with INO, (Soldatović & Bugarčić, 2005) can be concluded that these N-bonding ligands are good nucleophiles. This small difference in the reactivity of N-bondining (INO, 5'-IMP and 5'-GMP) and S-bonding nucleophiles (GSH and L-methionine) is not usually.…”

“…N7 atom of 5'-GMP can substitute the molecule of thioethar. (Reedijk, 1999;Soldatović & Bugarčić, 2005) For these reasons the compounds of the type Pt-S(thioethers) are believe to be the reservoirs of "platinum complexes'' in the body, i.e. they are suitable intermediates in the reaction of Pt(II) complexes and DNA.…”

“…The Pt-S(thiol) bond can be terminated in the presents of compounds known as "rescue agentsʼn, which are compounds with sulphur and they are very strong nucleophiles (diethyldithiocarbamate, thiourea, thiosulfate, GSH, cysteine, biotin, etc.). (Jakupec et al, 2003;Fuertes et al, 2003;Soldatović & Bugarčić, 2005) Scheme 1. Schematic presentation of the levels of action of cisplatin in the cell and possible biological consequences.…”