Solution structure of a DNA duplex containing a cis-diammineplatinum(II) 1,3-d(GTG) intrastrand cross-link, a major adduct in cells treated with the anticancer drug carboplatin

Jan Maarten Teuben, Cornelia Bauer, Andrew H.J. Wang, Jan Reedijk

研究成果: 雜誌貢獻文章同行評審

73 引文 斯高帕斯(Scopus)

摘要

The platinum 1,3-d(GXG) intrastrand cross-link is one of the adducts formed in the reaction of the antitumor drug cisplatin with DNA, and in fact the major adduct found in cells treated with the cisplatin analogue carboplatin. To determine the 3D structure of this adduct, the duplex d(CTCTG*TG*TCTC). d(GAGACACAGAG)], where G*TG* denotes a platinum 1,3- intrastrand cross-link, was prepared and studied with high-resolution 1H NMR. The solution structure was determined using the SPEDREF protocol, which includes an iterative NOE-restrained refinement procedure. Calculated and recorded NOE spectra were found to be in good agreement (NMR R factor 22%). The studied duplex is more distorted from B-DNA than previously determined structures of the 1,2-d(GG) intrastrand adducts. The base pairing is lost for the 5'G*-C and the central T-A base pair in the G*TG* lesion, and the central thymine is extruded from the minor groove. To accommodate this lesion, the minor groove is widened, and the 5'-guanine ribose adopts an N- type conformation. The helix is unwound locally and is significantly bent toward the major groove. Significant difference between the structural distortion of the 1,3-d(GTG) cross-link and other Pt-DNA cross-links sheds new light on the observed differences in protein recognition of these lesions, and thus on the possible differences in mechanisms of action of the various Pt-DNA adducts formed in treatment with platinum anticancer complexes.

原文英語
頁(從 - 到)12305-12312
頁數8
期刊Biochemistry
38
發行號38
DOIs
出版狀態已發佈 - 9月 21 1999
對外發佈

ASJC Scopus subject areas

  • 生物化學

指紋

深入研究「Solution structure of a DNA duplex containing a cis-diammineplatinum(II) 1,3-d(GTG) intrastrand cross-link, a major adduct in cells treated with the anticancer drug carboplatin」主題。共同形成了獨特的指紋。

引用此