The first pure LambdaHT rotamer of a complex with a cis-[metal(nucleotide)2] unit: a cis-[Pt(amine)2(nucleotide)2] LambdaHT rotamer with unique molecular structural features.
cis-[PtA2(nucleotide)2] complexes (A2 stands for two amines or a diamine) have been extensively investigated as model compounds for key cisplatin-DNA adducts. All cis-[metal(nucleotide/nucleoside)2] complexes with guanine and related purines characterized in the solid state thus far have the DeltaHT conformation (head-to-tail orientation of the two bases and right-handed chirality). In sharp contrast, the LambdaHT conformation (left-handed chirality) dominates in acidic and neutral aqueous solutions of cis-[PtA2(5'-GMP)2] complexes. Molecular models and solution experiments indicate that the LambdaHT conformer is stabilized by 5'-phosphate/N1H hydrogen-bond interactions between cis nucleotides with the normal anti conformation. However, this evidence, while compelling, is indirect. At last, conditions have been defined to allow crystallization of this elusive conformer. The structure obtained reveals three unique features not present in all other cis-[PtA2(nucleotide)2] solid-state structures: a LambdaHT conformation, very strong hydrogen-bond interactions between the phosphate and N1H of cis nucleotides, and a very small dihedral angle between the planes of the two guanines lying nearly perpendicular to the coordination plane. These new results indicate that, because there are no local base-base repulsions precluding the LambdaHT conformer, global forces rather than local interactions account for the predominance of the DeltaHT conformer over the LambdaHT conformer in the solid state and in both inter- and intrastrand HT crosslinks of oligonucleotides and DNA.
Benedetti
Michele
M
Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università degli Studi di Lecce, Via Monteroni, 73100 Lecce, Italy.
Tamasi
Gabriella
G
Cini
Renzo
R
Marzilli
Luigi G
LG
Natile
Giovanni
G
D002945:Cisplatin / Q000138:chemical synthesis / Q000737:chemistry*; D018736:DNA Adducts / Q000138:chemical synthesis / Q000737:chemistry*; D006157:Guanosine Monophosphate / Q000138:chemical synthesis / Q000737:chemistry*; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D009711:Nucleotides / Q000138:chemical synthesis / Q000737:chemistry*; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D014961:X-Ray Diffraction
D018736:DNA Adducts; D009711:Nucleotides; D009944:Organoplatinum Compounds; C057270:cisplatin-DNA adduct; D006157:Guanosine Monophosphate; D002945:Cisplatin