d(G_(3)AG_(2)T_(3)G_(3)AT)体外形成联锁型G-四链体 结构和稳定性

Structure and stability of interlocked G-quadruplexes formed by d(G_(3)AG_(2)T_(3)G_(3)AT)in vitro

G-四链体是由富含连续鸟嘌呤碱基串联的DNA或RNA单链折叠而成,具有维持染色体稳定、调控转录和翻译及其他生物学进程的重要意义。能够形成G-四链体结构的潜在碱基序列广泛存在人类基因组和mRNA中,尤其是端粒及基因启动子处。主要研究序列d(G_(3)AG_(2)T_(3)G_(3)AT)分别在钠和钾离子条件下形成联锁型G-四链体结构的不同特性。结果表明:该序列在钾离子溶液中先形成了动力学有利结构,随后自发转换为具有超高热稳定性的热力学稳定结构;钠离子条件下预先形成的结构,经过后续钾离子滴定可以直接转换为更稳定的钾离子热力学稳定结构。由于联锁型G-四链体良好的水溶性、生物相容性以及超高的热稳定性,它在自组装纳米材料领域具有潜在的应用前景。

The single stranded DNA or RNA sequences having rich stretches of consecutive guanines can fold into four-stranded structures known as G-quadruplexes,which play crucial roles in chromosomal maintenance,transcription and translation,as well as other biological processes.The putative G-quadruplex-forming sequences are wildly spread among the human genome and mRNA,especially more frequent in the telomere and promoters.Here,we focused on the different characteristics of the interlocked G-quadruplexes adopted by sequence d(G_(3)AG_(2)T_(3)G_(3)AT)in the presence of sodium and potassium ions,respectively.The experimental results showed that d(G_(3)AG_(2)T_(3)G_(3)AT)at first folded into a kinetically favorable conformation in K+solution,and then spontaneously converted to a thermodynamically stable conformation with an extremely high thermal stability.Secondly,upon K+ion titration,the interlocked G-quadruplex structure even well pre-folded in an excessive amount of Na+still enabled a ready conversion to the thermodynamically stable conformation ultimately stabilized by K+.This interlocked G-quadruplex will be expected applicable in the field of nanomaterial due to its considerable water-solubility,biocompatibility and extreme stability.