Platinum(II) binding to N7 and N1 of guanine and a model for a purine-N1,pyrimidine-N3 cross-link of cisplatin in the interior of a DNA duplex

1990 ◽  
Vol 29 (7) ◽  
pp. 1417-1422 ◽  
Author(s):  
Gudrun Frommer ◽  
Helmut Schoellhorn ◽  
Ulf Thewalt ◽  
Bernhard Lippert
Keyword(s):  
Cross Link ◽  
Dna Duplex

scholarly journals Solution Structures of a DNA Dodecamer Duplex with and without a Cisplatin 1,2-d(GG) Intrastrand Cross-Link:  Comparison with the Same DNA Duplex Containing an Oxaliplatin 1,2-d(GG) Intrastrand Cross-Link†,‡

Biochemistry ◽  
2007 ◽  
Vol 46 (22) ◽  
pp. 6477-6487 ◽  
Author(s):  
Yibing Wu ◽  
Debadeep Bhattacharyya ◽  
Candice L. King ◽  
Irene Baskerville-Abraham ◽  
Sung-Ho Huh ◽  
...  
Keyword(s):  
Cross Link ◽  
Dna Duplex ◽  
Solution Structures ◽  
Dna Dodecamer

scholarly journals 2.4-Å Crystal Structure of the Asymmetric Platinum Complex {Pt(ammine)(cyclohexylamine)}2+Bound to a Dodecamer DNA Duplex

2002 ◽  
Vol 277 (51) ◽  
pp. 49743-49749 ◽  
Author(s):  
Adam P. Silverman ◽  
Weiming Bu ◽  
Seth M. Cohen ◽  
Stephen J. Lippard
Keyword(s):  
Crystal Structure ◽  
Active Form ◽  
Platinum Complex ◽  
Chair Conformation ◽  
Phase Iii ◽  
Cancer Drug ◽  
Bend Angle ◽  
Cross Link ◽  
Dna Duplex ◽  
Cross Links

cis-trans-cis-Ammine(cyclohexylamine)diacetatodichloroplatinum(IV) is an oral analog of the platinum anti-cancer drug cisplatin that is currently in phase III clinical trials. Its active form, {Pt(ammine)(cyclohexylamine)}2+, binds to DNA similarly to cisplatin, forming intra- and interstrand cross-links between adjacent purine bases. Since {Pt(ammine)(cyclohexylamine)}2+contains two different ligands, it can form two isomeric 1,2-d(GpG) intrastrand cross-links. Here we report the 2.4-Å resolution x-ray crystal structure of the major adduct between {Pt(ammine)(cyclohexylamine)}2+and a DNA dodecamer, using the same sequence as previously reported for crystal structures of cisplatin-DNA (Takahara, P. M., Rosenzweig, A. C., Frederick, C. A., and Lippard, S. J. (1995)Nature377, 649–652) and oxaliplatin-DNA (Spingler, B., Whittington, D. A., and Lippard, S. J. (2001)Inorg. Chem.40, 5596–5602). Both duplexes in the asymmetric unit contain 1,2-intrastrand cross-links in which the cyclohexylamine ligand is directed toward the 3′-end of the platinated strand. The chair conformation of the cyclohexyl group is clearly resolved. Platination distorts the duplex, resulting in a global bend angle of about 38oand a dihedral angle between platinated guanine bases of ∼31o. Both end-to-end and end-to-groove packing interactions occur in the crystal lattice, the latter positioned in the minor groove across from the site of the platinum cross-link. A high degree of homology observed between this structure and the previously reported platinum-DNA structures suggests that these platinum complexes distort the DNA duplex in a very similar manner. These results suggest that differences in activity between these drugs are unlikely to result from gross conformational distortions in DNA structure following platinum intrastrand cross-link formation.

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