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 PtA2AmCl where A2=(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 Tm of the oligonucleotide by 2-11.5 degrees C while platination with the N7-guanosine complexes led to a rise in the melting temperature of the oligonucleotides by 4.5 degrees C. 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 Tm and CD spectra; the sugar moiety contributes to the stability of the double helix, probably through the formation of hydrogen bonds.
Peleg-Shulman
T
T
Department of Medicinal Chemistry, School of Pharmacy, The Hebrew University of Jerusalem, Israel.
Katzhendler
J
J
Gibson
D
D
D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism; D002942:Circular Dichroism; D018736:DNA Adducts / Q000737:chemistry; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry* / Q000378:metabolism*; D017671:Platinum Compounds / Q000737:chemistry* / Q000378:metabolism*; D014466:Ultraviolet Rays
D000970:Antineoplastic Agents; D018736:DNA Adducts; D009841:Oligonucleotides; D017671:Platinum Compounds