Smith F W, Schultze P, Feigon J
Department of Chemistry and Biochemistry, University of California, Los Angeles 90095, USA.
Structure. 1995 Oct 15;3(10):997-1008. doi: 10.1016/s0969-2126(01)00236-2.
Oligonucleotides containing the guanine-rich telomeric sequence of Oxytricha chromosomes (dT4G4) have previously been shown to form DNA quadruplexes comprising guanine quartets stabilized by cations. Two different structures have been reported for both d(G4T4G4) (Oxy1.5) and d(G4T4G4T4G4T4G4) (Oxy3.5).
Here we present the solution structure of a uracil- and inosine-containing derivative of Oxy3.5, d(G4TUTUG4T4G4UUTTG3I) (Oxy3.5-U4128), determined using two-dimensional 1H and 31P NMR techniques. This oligonucleotide forms a unimolecular quadruplex that is very similar to the dimeric Oxy1.5 solution structure, in that it contains a loop spanning the diagonal of an end quartet. The groove widths, strand polarities, and positions of the syn bases along the G4 tracts and within the quartets are all as reported for Oxy1.5. The first and third pyrimidine tracts form parallel loops spanning a wide groove and a narrow groove respectively.
Both Oxy3.5 and Oxy3.5-U(4)128 form unimolecular quadruplexes in solution with a diagonal central T4 loop. These results conflict with those reported for d(G4TUTUG4TTUUG4UUTTG4) in solution, in which the central loop spans a wide groove.
含有嗜热四膜虫染色体富含鸟嘌呤的端粒序列的寡核苷酸（dT4G4）先前已被证明可形成由阳离子稳定的包含鸟嘌呤四联体的DNA四链体。对于d(G4T4G4)（Oxy1.5）和d(G4T4G4T4G4T4G4)（Oxy3.5），已经报道了两种不同的结构。
在此，我们展示了使用二维1H和31P NMR技术确定的Oxy3.5的含尿嘧啶和次黄嘌呤衍生物d(G4TUTUG4T4G4UUTTG3I)（Oxy3.5-U4128）的溶液结构。该寡核苷酸形成单分子四链体，与二聚体Oxy1.5溶液结构非常相似，因为它包含一个跨越末端四联体对角线的环。沿着G4链和四联体内部的沟宽、链极性以及顺式碱基的位置均与Oxy1.5报道的一致。第一个和第三个嘧啶链分别形成跨越宽沟和窄沟的平行环。
Oxy3.5和Oxy3.5-U(4)128在溶液中均形成具有对角中心T4环的单分子四链体。这些结果与溶液中d(G4TUTUG4TTUUG4UUTTG4)报道的结果相矛盾，其中中心环跨越宽沟。
