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含有修饰碱基对的RNA双链体在寡核糖核苷酸内部和末端位置的热稳定性。

The thermal stability of RNA duplexes containing modified base pairs placed at internal and terminal positions of the oligoribonucleotides.

作者信息

Ziomek Krzysztof, Kierzek Elzbieta, Biała Ewa, Kierzek Ryszard

机构信息

Institute of Bioorganic Chemistry, Polish Academy of Sciences, 60-704 Poznañ, Noskowskiego 12/14, Poland.

出版信息

Biophys Chem. 2002 Jun 19;97(2-3):233-41. doi: 10.1016/s0301-4622(02)00074-1.

Abstract

The presence of various modifications within oligomers changes their thermodynamic stability. To get more systematic data, we measured effects of 5- and 6-substituted uridine on thermal stability of (AUCU(Mod.)AGAU)2 and (AUCUAGAU(Mod.))2. Collected results lead to the following conclusions: (i) 5-halogenated and 5-alkylated substituents of the uridine affect thermal stability of the RNA duplexes differently. Moreover, the 5-fluorouridine changes stability of the RNA duplexes opposite to remaining 5-halogenouridines; (ii) for oligomers containing 5-chloro, 5-bromo or 5-iodouridine stronger hydrogen bond formed between oxygen-4 of the 5-halogenated uracil and 6-amino group of the adenine is presumably responsible for stabilizing effect; (iii) placing of A-U(5R) base pairs closer to the end of the duplex enhance thermal stability relatively to oligomer with central position of this base pair; (iv) the effects of 5-substituents are additive, particularly for substituents which stabilize RNA duplexes; (v) 6-methyluridines (N1 and N3 isomers) as well as 3N-methyluridine present at internal position of A-U(Mod.) inhibit duplexes formation; (vi) 6-methyluridines (N1 and N3 isomers) as well as 3N-methyluridine placed as terminal base pairs stabilize the duplexes mostly via 3'-dangling end effect.

摘要

寡聚物中各种修饰的存在会改变其热力学稳定性。为了获得更系统的数据,我们测量了5-和6-取代尿苷对(AUCU(Mod.)AGAU)2和(AUCUAGAU(Mod.))2热稳定性的影响。收集到的结果得出以下结论:(i)尿苷的5-卤代和5-烷基取代基对RNA双链体热稳定性的影响不同。此外,5-氟尿苷改变RNA双链体稳定性的方式与其余5-卤代尿苷相反;(ii)对于含有5-氯、5-溴或5-碘尿苷的寡聚物,5-卤代尿嘧啶的氧-4与腺嘌呤的6-氨基之间形成的更强氢键可能是其稳定作用的原因;(iii)相对于该碱基对位于中心位置的寡聚物,将A-U(5R)碱基对放置得更靠近双链体末端会提高热稳定性;(iv)5-取代基的影响是累加的,特别是对于稳定RNA双链体的取代基;(v)位于A-U(Mod.)内部位置的6-甲基尿苷(N1和N3异构体)以及3N-甲基尿苷会抑制双链体的形成;(vi)作为末端碱基对放置的6-甲基尿苷(N1和N3异构体)以及3N-甲基尿苷主要通过3'-悬垂末端效应使双链体稳定。

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