Structural polymorphism in a tubercidin analogue of the DNA double helix

• Published in: Biophysical chemistry 1998-02, Vol.70 (2), p.161-172
• Main Authors: Pope, Lisa H, Shotton, Mark W, Forsyth, Trevor, Hughes, Darren J, Denny, Richard C, Fuller, Watson
• Format: Article
• Language: English
• Subjects: 7-Deazaadenine; Daresbury synchrotron radiation source (SRS); Deoxytubercidin; DNA; DNA - chemistry; DNA - metabolism; DNA–drug interactions; High-angle X-ray fibre diffraction; Molecular Conformation; Molecular Structure; Nucleic Acid Conformation; Poly dA-dT - chemistry; Poly dA-dT - metabolism; Polymers - chemistry; Tubercidin; Tubercidin - chemistry; Tubercidin - metabolism; X-Ray Diffraction - instrumentation
• ISSN: 0301-4622; 1873-4200
• DOI: 10.1016/S0301-4622(97)00132-4

A high-angle X-ray fibre diffraction study of a tubercidin analogue of the poly[d(A-T)]·poly[d(A-T)] DNA double helix has been carried out using station 7.2 at the Daresbury Laboratory synchrotron radiation source. The polymer has been studied for a wide range of salt strengths and hydration conditions and exhibits conformational polymorphism that is quite distinct from that observed for the unmodified polymer. The replacement of deoxyadenosine by deoxytubercidin in the polynucleotide causes only slight alterations to the structure of A-DNA, but significantly alters the structure of the B conformation. Additionally, the modified polymer does not, in any conditions yet identified, adopt the D conformation. In conditions which would normally favour the D conformation of poly[d(A-T)]·poly[d(A-T)], the modified polymer adopts an unusual conformation which is designated here as the K conformation. These observations are important for an understanding of major groove interactions involved in the stabilisation of particular DNA conformations and also more generally for an insight into the pharmacological activity of tubercidin which following its incorporation into nucleic acids may cause stereochemical distortions of the DNA double helix.