X-Ray structure of cytotoxic trans-[PtCl(2)(dimethylamine)(isopropylamine)]: interstrand cross-link efficiency, DNA sequence specificity, and inhibition of the B-Z transition.
We report here the X-ray structure of cytotoxic trans-¿PtCl(2)(dimethylamine)(isopropylamine). This trans-platinum compound crystallizes in the monoclinic system, with Z = 8, in the spatial group C2/c with unit cell parameters a = 19.862(17) A, b = 6. 581(3) A, c = 18.563(3) A, alpha = 90 degrees, beta = 119.16(3) degrees, gamma = 90 degrees, V = 2119(2) A(3), rho = 2.321 Mg/m(3), R = 0.0505, and R(w) = 0.1166 on the basis of 2339 independent reflections. To our knowledge this is the first report of the crystal structure of a biologically active trans-platinum compound containing different aliphatic amines. The DNA binding mode of trans-¿PtCl(2)(dimethylamine)(isopropylamine) may be a consequence of the spatial disposition of the dimethylamine and isopropylamine ligands around the trans-Pt(II) center. We have found that trans-¿PtCl(2)(dimethylamine)(isopropylamine) readily forms DNA interstrand cross-links. In addition, the compound shows binding affinity toward alternating purine-pyrimidine sequences and inhibits the B-Z transition. These particular DNA binding properties might be related to the capacity of trans-¿PtCl(2)(dimethylamine)(isopropylamine) for inducing some selective killing in a H-ras overexpresssing cell line.
Pérez
J M
JM
Departamento de Química Inorgánica, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
Montero
E I
EI
González
A M
AM
Solans
X
X
Font-Bardia
M
M
Fuertes
M A
MA
Alonso
C
C
Navarro-Ranninger
C
C
D000970:Antineoplastic Agents / Q000737:chemistry*; D002942:Circular Dichroism; D003432:Cross-Linking Reagents / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry*; D004278:DNA, Superhelical / Q000737:chemistry; D007700:Kinetics; D009944:Organoplatinum Compounds / Q000737:chemistry*; D011089:Polydeoxyribonucleotides / Q000737:chemistry; D012965:Sodium Chloride / Q000737:chemistry
D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D004278:DNA, Superhelical; D009944:Organoplatinum Compounds; D011089:Polydeoxyribonucleotides; C122083:dichloro(isopropylamine)(dimethylamine)platinum(II); C019530:poly(dC-dG); D012965:Sodium Chloride; D004247:DNA