Interactions of cis- and trans-platinum(II) complexes with dehydrogenase enzymes in the presence of different mono- and polynucleotides: evidence for a ternary complex.
The inhibition of several dehydrogenase enzymes by cis- and trans-Pt(NH3)2Cl2 have been measured in the presence of baker yeast ribonucleic acid (RNA), calf thymus and salmon sperm deoxyribonuclic acid (DNA) and several mononucleotides (AMP and ATP). The binding constants for the interaction of the platinum complexes to the nucleotides have been calculated and a comparison of those values to the previously calculated platinum complex-enzyme binding constants strongly suggest that platinum compounds are more tightly bound to the enzymes. The binding of the platinum complexes to most of the enzymes was decreased in the presence of any nucleotide, yet it was observed that when using rabbit muscle (M4) lactate dehydrogenase the mononucleotides reduced the binding to a lesser degree while the polynucleotides actually enhanced the platinum-enzyme interaction. The implications of these interactions are discussed.
D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D002945:Cisplatin / Q000378:metabolism / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors*; D008291:Malate Dehydrogenase / Q000037:antagonists & inhibitors*; D009711:Nucleotides / Q000378:metabolism*; D011485:Protein Binding; D012313:RNA / Q000378:metabolism; D013237:Stereoisomerism
D007527:Isoenzymes; D009711:Nucleotides; D000249:Adenosine Monophosphate; D012313:RNA; D000255:Adenosine Triphosphate; D004247:DNA; D007770:L-Lactate Dehydrogenase; D008291:Malate Dehydrogenase; D002945:Cisplatin