Antitumor Drug Nogalamycin Binds DNA in Both Grooves Simultaneously: Molecular Structure of Nogalamycin-DNA Complex

Yen Chywan Liaw, Yi Gui Gao, Howard Robinson, Gijs A. van der Marel, Jacques H. van Boom, Andrew H.J. Wang

研究成果: 雜誌貢獻文章同行評審

104 引文 斯高帕斯(Scopus)

摘要

The three-dimensional molecular structures of the complexes between an interesting antitumor drug, nogalamycin, and two DNA hexamers, d[CGT(pS)ACG] and d[m5CGT(pS)Am5CG], were determined at high resolution by X-ray diffraction analyses. Two nogalamycins bind to the DNA double helix in a 2:1 ratio with the aglycon chromophore intercalated between the CpG steps at both ends of the helix. The nogalose and aminoglucose sugars lie in the minor and major grooves, respectively, of the distorted B-DNA double helix. The binding of nogalamycin to DNA requires that the base pairs in DNA open up transiently to allow the bulky sugars to go through. Specific hydrogen bonds are found in the complex between the drug and guanine bases. We suggest that nogalamycin may prefer GC sequences embedded in a stretch of AT sequences.

原文英語
頁(從 - 到)9913-9918
頁數6
期刊Biochemistry
28
發行號26
DOIs
出版狀態已發佈 - 1989
對外發佈

ASJC Scopus subject areas

  • 生物化學

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