Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow Print PDF (264K) Freely available
Right arrow Supplementary Material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (13)
Right arrowRequest Permissions
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Temperini, C.
Right arrow Articles by Ughetto, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Temperini, C.
Right arrow Articles by Ughetto, G.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Nucleic Acids Research, 2003, Vol. 31, No. 5 1464-1469
© 2003 Oxford University Press

The crystal structure of the complex between a disaccharide anthracycline and the DNA hexamer d(CGATCG) reveals two different binding sites involving two DNA duplexes

Claudia Temperini, Luigi Messori, Pierluigi Orioli, Cristina Di Bugno1, Fabio Animati1 and Giovanni Ughetto*,2

Department of Chemistry, University of Florence, via della Lastruccia 3, Sesto F.no (FI), Italy, 1 Menarini Ricerche SpA, Pisa, Italy and 2 Istituto di Cristallografia, CNR, 00016 Monterotondo Stazione, Italy

*To whom correspondence should be addressed. Tel: +39 0 6 90625142; Fax: +39 0 6 90672630; Email: giovanni.ughetto{at}ic.cnr.it

The crystal structure of the complex formed between the anthracycline antibiotic 3'-deamino-3'- hydroxy-4'-(O-L-daunosaminyl)-4-demethoxydoxo rubicin (MEN 10755), an active disaccharide analogue of doxorubicin, and the DNA hexamer d(CGATCG) has been solved to a resolution of 2.1 Å. MEN 10755 exhibits a broad spectrum of antitumor activities, comparable with that of the parent compound, but there are differences in the mechanism of action as it is active in doxorubicin-resistant tumors and is more effective in stimulating topoisomerase DNA cleavage. The structure is similar to previously crystallised anthracycline– DNA complexes. However, two different binding sites arise from drug intercalation so that the two halves of the self-complementary duplex are no longer equivalent. In one site both sugar rings lie in the minor groove. In the other site the second sugar protrudes out from the DNA helix and is linked, through hydrogen bonds, to guanine of a symmetry-related DNA molecule. This is the first structure of an anthracycline–DNA complex where an interaction of the drug with a second DNA helix is observed. We discuss the present findings with respect to the relevance of the amino group for DNA binding and to the potential role played by the second sugar in the interactions with topoisomerases or other cellular targets.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Pharmacol. Rev.Home page
G. Minotti, P. Menna, E. Salvatorelli, G. Cairo, and L. Gianni
Anthracyclines: Molecular Advances and Pharmacologic Developments in Antitumor Activity and Cardiotoxicity
Pharmacol. Rev., June 1, 2004; 56(2): 185 - 229.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.