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 duple x oligonucleotide by means of CD and UV melting profiles. We studied severa l 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-guano sine, and 9-ethyl-guanine. Platination by the N1-4-methyl-pyridine and 9-et hyl-guanine complexes led to a decrease in the T-m of the oligonucleotide b y 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 pronou nced effect on both the melting curve and the CD spectrum. The cis isomer w as found to have a more destabilizing effect than its trans counterpart. Th is indicates that the cis geometry in fact forces a greater structural cons traint on the backbone of the double helix. We have also found that the sug ar of the guanosine has a significant influence on both the T-m and CD spec tra; the sugar moiety contributes to the stability of the double helix, pro bably through the formation of hydrogen bonds. (C) 2000 Elsevier Science S. A. All rights reserved.