Effects of monofunctional platinum binding on the thermal stability and conformation of a self-complementary 22-mer

We investigated the effect of various monofunctional platinum complexes on the thermal stability and conformation of a self-complementary 22-mer duplex oligonucleotide by means of CD and UV melting profiles. We studied several families of triamine complexes of the general formula PtA(2)AmCl where A(2)=(NH3)(2) and ethylenediamine and where Am=N1-4-methyl-pyridine, N7-guanosine, and 9-ethyl-guanine. Platination by the N1-4-methyl-pyridine and 9-ethyl-guanine complexes led to a decrease in the T-m of the oligonucleotide by 2-11.5 degreesC while platination with the N7-guanosine complexes led to a rise in the melting temperature of the oligonucleotides by 4.5 degreesC. A similar inverse correlation between the two groups of platinum compounds was found in the CD spectra. In all cases, the cis isomer had a more pronounced effect on both the melting curve and the CD spectrum. The cis isomer was found to have a more destabilizing effect than its trans counterpart. This indicates that the cis geometry in fact forces a greater structural constraint on the backbone of the double helix. We have also found that the sugar of the guanosine has a significant influence on both the T-m and CD spectra; the sugar moiety contributes to the stability of the double helix, probably through the formation of hydrogen bonds. (C) 2000 Elsevier Science S.A. All rights reserved.