What affects the effect of 2′-alkoxy modifications?: 1.: Stabilization effect of 2′-methoxy substitutions in uniformly modified DNA oligonucleotides
What affects the effect of 2′-alkoxy modifications?: 1.: Stabilization effect of 2′-methoxy substitutions in uniformly modified DNA oligonucleotides
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DOI：
10.1021/bi972995c
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发表时间：
1998-05-12
期刊：
影响因子：
2.9
通讯作者：
Freier, SM
中科院分区：
文献类型：
--
作者：
Lesnik, EA;Freier, SM
测定了具有均匀2 ′-甲氧基修饰的DNA链（D ′ R和RD ′）、它们的未修饰的DNA：RNA对应物（DR和RD）和对应的RNA：RNA（RR）双链体对于具有不同GC和脱氧嘧啶（dPy）含量的六个序列的热稳定性。2 '-甲氧基修饰的总稳定化效果之间的线性相关性（Δ Δ G度（37）（D 'R-DR））和与RR对应物相比的相应未修饰杂交体的相对稳定性（Δ Δ G度（37）（RR-DR））表明，“母体”未修饰的杂合物的初始构象和热力学状态控制2 '-甲氧基的作用，并且可能是其他2'-甲氧基。烷氧基）修饰，其作用机制包括产生RNA样A型双链体的S -> N构象转变。我们还发现了总效应的“疏水”部分（Δ Δ G度（37）（D 'R-RR））与修饰的DNA链中的dA分数之间的相关性，这表明2'-甲氧基的“疏水”效应主要来自残基内空间效应，其增加了修饰的糖环的刚性。观察到的相关性使我们能够预测具有2 '-甲氧基修饰的DNA链的杂交体对于任何序列的稳定性，除了具有（dU）（10）和（dA）（10）串的序列。
The thermostability of hybrid duplexes with uniformly 2'-methoxy modified DNA strands (D'R and RD'), their unmodified DNA:RNA counterparts (DR and RD), and corresponded RNA:RNA (RR) duplexes for six sequences with different GC and deoxypyrimidine (dPy) content was measured. The linear correlation between the total stabilization effect of 2'-methoxy modifications (Delta Delta G degrees(37)(D'R-DR)) and the relative stability of corresponding unmodified hybrids compared to the RR counterparts (Delta Delta G degrees(37)(RR-DR)) suggests that the initial conformational and the thermodynamic state of the "parent" unmodified hybrid governs the effect of 2'-methoxy land may be other 2'-alkoxy) modifications whose mechanism of action includes an S --> N conformational shift resulting in an RNA-like A-form duplex. We also found a correlation between the "hydrophobic" part of the total effect (Delta Delta G degrees(37) (D'R-RR)) and the dA fraction in the modified DNA strand, suggesting that the "hydrophobic" effect of the 2'-methoxy groups results mainly from intraresidue steric effects increasing rigidity of the modified sugar rings. The correlations observed enabled us to predict the stability of hybrids with 2'-methoxy modified DNA strands for any sequence except for sequences with (dU)(10) and (dA)(10) strings.