Recognition of GC base pairs by triplex forming oligonucleotides containing nucleosides derived from 2-aminopyridine
Recognition of GC base pairs by triplex forming oligonucleotides containing nucleosides derived from 2-aminopyridine
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DOI：
10.1093/nar/25.24.4891
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发表时间：
1997-12-15
影响因子：
14.9
通讯作者：
Fox, KR
中科院分区：
文献类型：
--
作者：
Cassidy, SA;Slickers, P;Fox, KR
我们尝试通过使用含有2-氨基-5-(2-脱氧-D-呋喃核糖基)吡啶(AP)的分子间三链体作为2'-脱氧胞苷(dC)的类似物来减轻鸟嘌呤三联体识别的pH依赖性，我们发现对于AP的β-端基异构体，(AP)(6)T-6和靶位点G(6)A(6).T6C6之间的复合物是稳定的，在 pH 5.0 时，寡核苷酸浓度低至 0.25 μM，即可产生清晰的 DNase I 足迹，而 50 μM C6T6 对切割模式没有影响，该复合物在 pH 6.5 下仍然稳定，产生 1 μM 寡核苷酸的足迹。含有AP的α-端基异构体的寡核苷酸的效果比β-端基异构体低得多，尽管在某些情况下它们比未修饰的寡核苷酸更稳定。对一系列含有AP的三链体进行的分子动力学研究结果合理化了观察到的氢键行为稳定性行为。
We have attempted to alleviate the pH dependency of tripler recognition of guanine by using intermolecular triplexes containing 2-amino-5-(2-deoxy-D-ribofuranosyl)pyridine (AP) as an analogue of 2'-deoxycytidine (dC), We find that for the beta-anomer of AP, the complex between (AP)(6)T-6 and the target site G(6)A(6).T6C6 is stable, generating a clear DNase I footprint at oligonucleotide concentrations as low as 0.25 mu M at pH 5.0, in contrast to 50 mu M C6T6 which has no effect on the cleavage pattern, This complex is still stable at pH 6.5 producing a footprint with 1 mu M oligonucleotide. Oligonucleotides containing the alpha-anomer of AP are much less effective than the beta-anomer, though in some instances they are more stable than the unmodified oligonucleotides, The results of molecular dynamics studies on a range of AP-containing triplexes has rationalized the observed stability behaviour in terms of hydrogen-bonding behaviour.