Pyrimidine morpholino oligonucleotides form a stable triple helix in the absence of magnesium ions
Pyrimidine morpholino oligonucleotides form a stable triple helix in the absence of magnesium ions
复制标题
DOI：
10.1006/bbrc.2000.2438
复制
发表时间：
2000-04-13
影响因子：
3.1
通讯作者：
Mergny, JL
中科院分区：
文献类型：
--
作者：
Lacroix, L;Arimondo, PB;Mergny, JL
寡核苷酸可以通过形成一个局部三螺旋作为序列特异性DNA配体。为了形成更稳定的三螺旋结构或防止其在细胞中降解，通常使用在主链或碱基水平上进行修饰的寡核苷酸类似物。近年来，Morpholino寡核苷酸作为一种很有前途的反义修饰物出现。我们在这里报告了一项研究，表明了三螺旋结构的可能性与morpholino嘧啶TFO及其与磷酸二酯和磷酰胺寡核苷酸的比较。在中性pH值和高镁离子浓度（10 mM）下，磷酰胺寡聚物形成最稳定的三螺旋结构，而在镁离子不存在但生理单价阳离子浓度（0.14 M）下，只有morpholino寡核苷酸形成稳定的三螺旋结构。据我们所知，这是首次报道由非带电寡核苷酸第三链（morpholino寡核苷酸）和DNA双链构成的稳定的嘧啶基序三螺旋结构。我们在这里表明，由morpholino低聚物形成的结构是真正的三螺旋结构，高浓度的钾离子或二价阳离子（Mg2+）会使其不稳定。(C) 2000年学术出版社。
Oligonucleotides can be used as sequence-specific DNA ligands by forming a local triple helix. In order to form more stable triple-helical structures or prevent their degradation in cells, oligonucleotide analogues that are modified at either the backbone or base level are routinely used. Morpholino oligonucleotides appeared recently as a promising modification for antisense applications. We report here a study that indicates the possibility of a triple helix formation with a morpholino pyrimidine TFO and its comparison with a phosphodiester and a phosphoramidate oligonueleotide. At a neutral pH and in the presence of a high magnesium ion concentration (10 mM), the phosphoramidate oligomer forms the most stable triple helix, whereas in the absence of magnesium ion but at a physiological monovalent cation concentration (0.14 M) only morpholino oligonucleotides form a stable triplex. To our knowledge, this is the first report of a stable triple helix in the pyrimidine motif formed by a noncharged oligonucleotide third strand (the morpholino oligonucleotide) and a DNA duplex. We show here that the structure formed with the morpholino oligomer is a bona fide triple helix and it is destabilized by high concentrations of potassium ions or divalent cations(Mg2+). (C) 2000 Academic Press.