Conformer distribution in (cis-1,4-DACH)bis(guanosine-5'-phosphate)platinum(II) adducts: a reliable model for DNA adducts of antitumoral cisplatin.
In [PtCl2(cis-1,4-DACH)] (DACH = diaminocyclohexane), the N-Pt-N bite angle (> or =97 degrees , as determined by X-ray diffraction analysis) is much larger than those found in other Pt complexes with bidentate diamines or in cisplatin (approximately 91 degrees ). Hence, the possibility exists that in (cis-1,4-DACH)PtG 2 adducts, rotation of the G's around the Pt-N7 bonds is slowed enough to allow observation of different conformers. In accord with this prevision, decreasing the temperature to 238 K enabled us to observe different conformers of (cis-1,4-DACH)Pt(5'-GMP) 2 (GMP = guanosine monophosphate). This observation is the first case in which such conformers for a platinum derivative with primary diamines and untethered guanines have been resolved and represents the closest model to clinically effective cisplatin obtained to date. We also found that the presence of the 1,4-DACH ligand increased the intensity of the circular dichroism signal stemming from the dominance of an HT conformer (DeltaHT in the adduct with 3'-GMPs and LambdaHT in the adduct with 5'-GMPs).
Ranaldo
Rosa
R
Dipartimento Farmaco-Chimico, Università degli Studi di Bari, Via E. Orabona 4, 70125 Bari, Italy.
Margiotta
Nicola
N
Intini
Francesco P
FP
Pacifico
Concetta
C
Natile
Giovanni
G
D000970:Antineoplastic Agents / Q000737:chemistry*; D002942:Circular Dichroism; D002945:Cisplatin / Q000737:chemistry*; D018360:Crystallography, X-Ray; D018736:DNA Adducts / Q000737:chemistry*; D006151:Guanosine / Q000031:analogs & derivatives* / Q000737:chemistry; D006157:Guanosine Monophosphate / Q000737:chemistry; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D009711:Nucleotides / Q000737:chemistry; D009944:Organoplatinum Compounds / Q000737:chemistry*; D012997:Solvents; D013696:Temperature
D000970:Antineoplastic Agents; D018736:DNA Adducts; D008024:Ligands; D009711:Nucleotides; D009944:Organoplatinum Compounds; D012997:Solvents; D006151:Guanosine; C068152:3'-guanylic acid; D006157:Guanosine Monophosphate; D002945:Cisplatin