The formation pathway of tetramolecular G-quadruplexes.

The formation pathway of tetramolecular G-quadruplexes.
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四分子G四链体的形成途径。

DOI:
10.1093/nar/gkm1050
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发表时间:
2008-02
影响因子:
14.9
通讯作者:
Leroy, Jean Louis
Leroy, Jean Louis
中科院分区:
生物学2区
文献类型:
--
作者:
Bardin, Caroline;Leroy, Jean Louis

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含有鸟苷链的寡核苷酸结合成由单价离子稳定的四聚体结构。为了描述导致四条相同链缔合的反应序列,我们通过NMR测量了(TGnT)4四链体(n = 3-6)的形成和解离速率、它们的解离常数和四链体形成的反应级数。四链体的形成率随盐浓度的增加,但弱依赖于反离子的性质(K+,Na+或Li+)。四链体形成的活化能为负值。四链体的寿命强烈增加的G-道的长度和更长的时间在K+溶液中比在Na+或Li+的解决方案。在0.125 M KCl溶液中,四链体形成的反应级数为3,在LiCl溶液中为4。动力学测量表明,四链体的形成进行一步一步地通过顺序链协会到双链体和三链体中间物种。在0.125 M KCl溶液中,三链体的形成是速率限制性的。在LiCl中,缔合过程的每一步都取决于链浓度。平行反应形成的完全匹配的典型的四链体可能会导致动力学捕获的失配的四链体,使典型的四链体实际上是不可访问的,特别是在低温下在KCl溶液中。
Oligonucleotides containing guanosine stretches associate into tetrameric structures stabilized by monovalent ions. In order to describe the sequence of reactions leading to association of four identical strands, we measured by NMR the formation and dissociation rates of (TGnT)4 quadruplexes (n = 3–6), their dissociation constants and the reaction orders for quadruplex formation. The quadruplex formation rates increase with the salt concentration but weakly depend on the nature (K+, Na+ or Li+) of the counter ions. The activation energies for quadruplex formation are negative. The quadruplex lifetimes strongly increase with the G-tract length and are much more longer in K+ solution than in Na+ or Li+ solutions. The reaction order for quadruplex formation is 3 in 0.125 M KCl and 4 in LiCl solutions. The kinetics measurements suggest that quadruplex formation proceeds step by step via sequential strand association into duplex and triplex intermediate species. Triplex formation is rate limiting in 0.125 M KCl solution. In LiCl, each step of the association process depends on the strand concentration. Parallel reactions to formation of the fully matched canonical quadruplex may result in kinetically trapped mismatched quadruplexes making the canonical quadruplex practically inaccessible in particular at low temperature in KCl solution.
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