INFLUENCE OF CIS-DIAMMINEDICHLOROPLATINUM(II) AND TRANS-DIAMMINEDICHLOROPLATINUM(II) BINDING ON THE HELIX-COIL TRANSITION OF DNAS WITH DIFFERENT GC CONTENT

The influence of cis-diamminedichloroplatinum(II) (cis-DDP) and trans- diamminedichloroplatinum (II) (trans-DDP) binding on the helix-coil tr ansition of DNAs with different GC composition is investigated experim entally and theoretically (26 less than or equal to GC less than or eq ual to 72%; 0.003 less than or equal to r(b) less than or equal to 3; where r(b) is the number of moles of bound DDP per mole of nucleotide) . In contrast to previous studies, it is demonstrated that cis-DDP inc reases the DNA melting temperature (T-m,) if GC content and r(b), are low enough. Stabilization occurs for r(b),= 0.003 if GC = 26% or 42%. Destabilization takes place for higher GC and r(b), values. Trans-DDP causes only stabilization independently of GC content if r(b),less tha n or equal to 0.3. For the highest GC content (72%), very low concentr ation (r(b),= 0.003) of both compounds gives rise to a strong shift of the melting temperature which is equal to -4.5 degrees C for cis-DDP and + 3.5 degrees C for trans-DDP. It is shown that well known bidenta te and monodentate, kinetically inert platinum binding cannot bring ab out such a strong T-m, alteration. Computer simulation of the helix-co il transition of DNA-ligand complexes is used to explain the observed effects. (C) 1998 Elsevier Science S.A. All rights reserved.