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- Title
Interactions with DNA Models of the Oxaliplatin Analog (cis -1,3-DACH)PtCl 2 †.
- Authors
Barbanente, Alessandra; Papadia, Paride; Di Cosola, Anna Maria; Pacifico, Concetta; Natile, Giovanni; Hoeschele, James D.; Margiotta, Nicola
- Abstract
It is generally accepted that adjacent guanine residues in DNA are the primary target for platinum antitumor drugs and that differences in the conformations of the Pt-DNA adducts can play a role in their antitumor activity. In this study, we investigated the effect of the carrier ligand cis-1,3-diaminocyclohexane (cis-1,3-DACH) upon formation, stability, and stereochemistry of the (cis-1,3-DACH)PtG2 and (cis-1,3-DACH)Pt(d(GpG)) adducts (G = 9-EthlyGuanine, guanosine, 5′- and 3′-guanosine monophosphate; d(GpG) = deoxyguanosil(3′-5′)deoxyguanosine). A peculiar feature of the cis-1,3-DACH carrier ligand is the steric bulk of the diamine, which is asymmetric with respect to the Pt-coordination plane. The (cis-1,3-DACH)Pt(5′GMP)2 and (cis-1,3-DACH)Pt(3′GMP)2 adducts show preference for the ΛHT and ∆HT conformations, respectively (HT stands for Head-to-Tail). Moreover, the increased intensity of the circular dichroism signals in the cis-1,3-DACH derivatives with respect to the analogous cis-(NH3)2 species could be a consequence of the greater bite angle of the cis-1,3-DACH carrier ligand with respect to cis-(NH3)2. Finally, the (cis-1,3-DACH)Pt(d(GpG)) adduct is present in two isomeric forms, each one giving a pair of H8 resonances linked by a NOE cross peak. The two isomers were formed in comparable amounts and had a dominance of the HH conformer but with some contribution of the ΔHT conformer which is related to the HH conformer by having the 3′-G base flipped with respect to the 5′-G residue.
- Subjects
OXALIPLATIN; LIGANDS (Chemistry); DNA; DNA adducts; STEREOCHEMISTRY; ANTINEOPLASTIC agents; DIAMINES
- Publication
International Journal of Molecular Sciences, 2024, Vol 25, Issue 13, p7392
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms25137392