STRUCTURAL POLYMORPHISM IN A TUBERCIDIN ANALOG OF THE DNA DOUBLE HELIX

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 so urce. 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 signifi cantly alters the structure of the B conformation. Additionally, the m odified polymer does not, in any conditions yet identified, adopt the D conformation. In conditions which would normally favour the D confor mation of poly[d(A-T)]. poly[d(A-T)], the modified polymer adopts an u nusual conformation which is designated here as the K conformation. Th ese observations are important for an understanding of major groove in teractions involved in the stabilisation of particular DNA conformatio ns and also more generally for an insight into the pharmacological act ivity of tubercidin which following its incorporation into nucleic aci ds may cause stereochemical distortions of the DNA double helix. (C) 1 998 Elsevier Science B.V.