A conformationally constrained nucleotide analogue controls the folding topology of a DNA G-quadruplex
A conformationally constrained nucleotide analogue controls the folding topology of a DNA G-quadruplex
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DOI：
10.1021/ja039192z
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发表时间：
2004-04-28
影响因子：
15
通讯作者：
Jarstfer, MB
中科院分区：
文献类型：
--
作者：
Dominick, PK;Jarstfer, MB
富含鸟嘌呤的DNA和RNA序列可以折叠成被称为G-四链的独特结构。根据链的平行或反平行性质以及寡核苷酸中存在的富含G的链的数量，G-四链体的结构可以分为几类。寡核苷酸与单链鸟嘌呤形成分子间平行的四聚体G-四链体。含有两个或两个以上碱基的鸟苷的寡核苷酸可以形成分子间反平行折叠二聚体和平行四聚体G-四聚体，而含有四个鸟苷的寡核苷酸既可以形成分子内平行结构，也可以形成反平行结构。分子内G-qaudruplex可以折叠成几种折叠拓扑，包括反平行交叉篮子、反平行椅子和平行螺旋桨。控制G-四链折叠的能力将使人们能够研究这些不同折叠拓扑的物理、生化和生物学性质。以前，已知的控制G-四链折叠拓扑的方法包括通过改变存在的一价和二价阳离子以及通过改变DNA序列来改变缓冲液。由于具有平行链的G-四链的G-四联体中的糖苷键是反构象的，我们推测，在富含G的序列中加入更喜欢糖苷键反构象的核苷类似物将增加平行G-四链体形成的偏好。正如预测的那样，通过将构象受限的核苷酸类似物2‘-O-4’-C-亚甲基连接的核糖核苷酸定位到DNA G-四链的特定位置，我们能够将G-四链的热力学有利结构从反平行结构转变为平行结构。
Guanine-rich DNA and RNA sequences can fold into unique structures known as G-quadruplexes. The structures of G-quadruplexes can be divided into several classes, depending on the parallel or antiparallel nature of the strands and the number of G-rich tracts present in an oligonucleotide. Oligonucleotides with single tracts of guanines form intermolecular parallel tetrameric G-quadruplexes. Oligonucleotides with two tracts of guanosines separated by two or more bases can form both intermolecular antiparallel fold-back dimeric and parallel tetrameric G-quadruplexes, and those with four tracts of guanosines can form both intramolecular parallel and antiparallel structures. Intramolecular G-qaudruplexes can fold into several folding topologies including antiparallel crossover basket, antiparallel chair, and parallel propeller. The ability to control the folding of G-quadruplexes would allow the physical, biochemical, and biological properties of these various folding topologies to be studied. Previously, the known methods to control the folding topology of G-quadruplexes included changing the buffer by varying the mono- and divalent cations that are present, and by changing the DNA sequence. Because the glycosidic bonds in the G-quartets of G-quadruplexes with parallel strands are in theanticonformation, we reasoned that incorporation of nucleoside analogues that prefer theanticonformation of the glycosidic bond into G-rich sequences would increase the preference for parallel G-quadruplex formation. As predicted, by positioning the conformationally constrained nucleotide analogue 2‘-O-4‘-C-methylene-linked ribonucleotide into specific positions of a DNA G-quadruplex we were able to shift the thermodynamically favored structure of a G-quadruplex from an antiparallel to a parallel structure.