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https://hdl.handle.net/2440/34475
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Type: | Journal article |
Title: | Structural investigation of the hedamycin:d(ACCGGT)2 complex by NMR and restrained molecular dynamics |
Author: | Owen, E. Burley, G. Carver, J. Wickham, G. Keniry, M. |
Citation: | Biochemical and Biophysical Research Communications, 2002; 290(5):1602-1608 |
Publisher: | Academic Press Inc |
Issue Date: | 2002 |
ISSN: | 0006-291X 1090-2104 |
Statement of Responsibility: | Elisabeth A. Owen, Glenn A. Burley, John A. Carver, Geoffrey Wickham and Max A. Keniry |
Abstract: | Hedamycin, a member of the pluramycin family of drugs, displays a range of biological responses including antitumor and antimicrobial activity. The mechanism of action is via direct interaction with DNA through intercalation between the bases of the oligonucleotide and alkylation of a guanine residue at 5'-PyG-3' sites. There appears to be some minor structural differences between two earlier studies on the interaction of hedamycin with 5'-PyG-3' sites. In this study, a high-resolution NMR analysis of the hedamycin:d(ACCGGT)2 complex was undertaken in order to investigate the effect of replacing the thymine with a guanine at the preferred 5'-CGT-3' site. The resultant structure was compared with earlier work, with particular emphasis placed on the drug conformation. The structure of the hedamycin:d(ACCGGT)2 complex has many features in common with the two previous NMR structures of hedamycin:DNA complexes but differed in the conformation and orientation of the N,N-dimethylvancosamine saccharide of hedamycin in one of these structures. The preferential binding of hedamycin to 5'-CG-3' over 5'-TG-3' binding sites is explained in terms of the orientation and location of the N,N-dimethylvancosamine saccharide in the minor groove. |
Keywords: | 2D NMR drug-DNA hedamycin oligonucleotide |
DOI: | 10.1006/bbrc.2002.6369 |
Description (link): | http://www.elsevier.com/wps/find/journaldescription.cws_home/622790/description#description |
Published version: | http://dx.doi.org/10.1006/bbrc.2002.6369 |
Appears in Collections: | Aurora harvest Chemistry and Physics publications |
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