Comparison of Cis‐ and Oxaliplatin‐induced Destabilization of 15‐mer DNA‐ and RNA Duplexes by Binding to Centrally Located GG‐ and GNG Sequences

Abstract

AbstractThermodynamic parameters are presented here illustrating the effects caused by the two anticancer active metal complexes cisplatin and oxaliplatin after introduction into four closely related RNA and DNA duplexes. The duplexes used are blunt end, fully complementary 15‐mer duplexes with a centrally located either GG‐ or GNG (here: N = T or U) binding site. For all duplexes, a common trend of reduced melting temperature was observed after platination. Analysis of the thermodynamic parameters for the duplex dissociation reactions showed good correlation between variations in melting temperatures (Tm) and ground state enthalpies (ΔH) in both DNA‐ and RNA duplexes. The melting temperatures of the native duplexes were found to be determined by their chemical nature, i.e. with observed Tm ‐values of ca. 50 °C for DNA and ca. 61 °C for RNA (CT = 2 μM and CNa+ = 129 mM, pH 6.3). Of the two types of nucleic acids, RNA is the one that exhibits the most pronounced sensitivity towards introduction of the platinum complexes, and with oxaliplatin as the more influential metalation reagent. Of note is that the thermal destabilization caused by oxaliplatin interacting with a centrally located GUG‐sequence results in a duplex stability below native DNA.