Structure of 11-deoxydaunomycin bound to DNA containing a phosphorothioate

Loren Dean Williams, Martin Egli, Giovanni Ughetto, Gijs A. van der Marel, Jacques H. van Boom, Gary J. Quigley, Andrew H.J. Wang, Alexander Rich, Christine A. Frederick

研究成果: 雜誌貢獻文章同行評審

35 引文 斯高帕斯(Scopus)


The anthracyclines form an important family of cancer chemotherapeutic agents with a strong dependence of clinical properties on minor differences in chemical structure. We describe the X-ray crystallographic solution of the three-dimensional structure of the anthracycline 11-deoxydaunomycin plus d(CGTsACG). In this complex, two drug molecules bind to each hexamer duplex. Both the drug and the DNA are covalently modified in this complex in contrast with the three previously reported DNA-anthracycline complexes. In the 11-deoxydaunomycin complex the 11 hydroxyl group is absent and a phosphate oxygen at the TpA step has been replaced by a sulfur atom leading to a phosphorothioate with absolute stereochemistry R. Surprisingly, removal of a hydroxyl group from the 11 position does not alter the relative orientation of the intercalated chromophore. However, it appears that the phosphorothioate modification influenced the crystallization and caused the 11-deoxydaunomycin-d(CGTsACG) complex to crystallize into a different lattice (space group P2) with different lattice contacts and packing forces than the nonphosphorothioated DNA-anthracycline complexes (space group P41212). In the minor groove of the DNA, the unexpected position of the amino-sugar of 11-deoxydaunomycin supports the hypothesis that in solution the position of the amino sugar is dynamic.

頁(從 - 到)313-320
期刊Journal of Molecular Biology
出版狀態已發佈 - 9月 20 1990

ASJC Scopus subject areas

  • 結構生物學
  • 分子生物學


深入研究「Structure of 11-deoxydaunomycin bound to DNA containing a phosphorothioate」主題。共同形成了獨特的指紋。