Hoogsteen versus Watson-Crick A-T basepairing in DNA complexes of a new group of ‘quinomycin-like’ antibiotics

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Abstract
The interaction of a new group of ‘quinomycin-like’ antibiotics with the DNA duplexes d(ACGT) 2 and d(GACGTC) 2 has been investigated in solution by 1 H NMR spectroscopy. By monitoring the intensity of intranucleotide base H6/H8 to deoxyribose H1'NOE cross-peaks we conclude that the terminal A-T basepairs flanking the CG bisintercalation site in the d(ACGT) 2 complex adopt the Hoogsteen bonding scheme, with the purine base in a syn conformation. By comparison in the d(GACGTC) 2 complex all glycosidic bond angles are anti , consistent with a preferred Watson-Crick basepairing scheme. Both DNA duplexes appear to be significantly unwound compared with the ligand-free DNAs. The data illustrate the influence of helical constraints on the stability of the Hoogsteen bonding scheme adjacent to the drug binding sites.