Certain platinum
diamine complexes have anticancer activity that results from of the formation
of DNA adducts. We are studying the
competition between protein and DNA adduct formation by platinum complexes
containing diamine ligands of different size to determine how the size affects
this competition. Two representative
complexes, Pt(en)Cl2 and Pt(Me4en)Cl2 (en = ethylenediamine, Me4en =
N,N,N’,N’-tetramethylethylenediamine) have been studied in our laboratory. These platinum complexes are treated with
silver nitrate to convert them to diaqua complexes; the diaqua forms are then
reacted with solutions containing N-AcMet and/or 5’-GMP, representative protein
and DNA targets, respectively. The
reactions are monitored by NMR spectroscopy, and the products are identified by
comparison to the NMR data of previously characterized complexes. As expected, the presence of additional bulk
slows reaction of the Pt(Me4en)(H2O)22+
complex with both targets. However, results
suggest that the bulk affects the relative rates with 5’-GMP and N-AcMet
differently.