Owen, ElisabethBurley, GlennCarver, JohnWickham, GeoffreyKeniry, Max2015-12-130006-291Xhttp://hdl.handle.net/1885/73107Hedamycin, 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: carbohydrate derivative; guanine; hedamycin; n,n dimethylvancosamine saccharide; thymine; unclassified drug; article; binding site; chromatophore; DNA drug complex; drug conformation; drug DNA interaction; molecular dynamics; nuclear magnetic resonance; n 2D NMR; Drug-DNA; Hedamycin; Oligonucleotide200210.1006/bbrc.2002.63692015-12-11