Insights into the reaction of transplatin with DNA and proteins: methionine-mediated formation of histidine-guanine trans-Pt(NH3)2 cross-links.

Simultaneous exposure of transplatin to polypeptides and DNA was mimicked by using a model peptide-oligonucleotide conjugate. Initially formed methionine-guanine chelates evolved into adducts with histidine-guanine trans-Pt(NH3)2 cross-links that differed in constitution and stability from those formed by reaction of the same conjugate with the anticancer drug cisplatin. This finding may be due to different capacities of the two diamminedichloroplatinum(II) complexes to interfere with biological processes and may explain their differing cytotoxicities.