Pope L H, Shotton M W, Forsyth T, Hughes D J, Denny R C, Fuller W
Physics Department, Keele University, Staffordshire, UK.
Biophys Chem. 1998 Feb 16;70(2):161-72. 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.
利用达累斯伯里实验室同步辐射源的7.2号实验站，对聚[d(A-T)]·聚[d(A-T)] DNA双螺旋的结核菌素类似物进行了高角度X射线纤维衍射研究。在广泛的盐浓度和水合条件下对该聚合物进行了研究，其呈现出的构象多态性与未修饰聚合物所观察到的情况截然不同。在多核苷酸中用脱氧结核菌素取代脱氧腺苷，只会使A-DNA的结构发生轻微改变，但会显著改变B构象的结构。此外，在尚未确定的任何条件下，修饰后的聚合物都不会采用D构象。在通常有利于聚[d(A-T)]·聚[d(A-T)]的D构象的条件下，修饰后的聚合物会采用一种不寻常的构象，在此处将其指定为K构象。这些观察结果对于理解特定DNA构象稳定过程中涉及的大沟相互作用很重要，并且更广泛地说，对于深入了解结核菌素的药理活性也很重要，因为结核菌素掺入核酸后可能会导致DNA双螺旋的立体化学扭曲。
