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具有不同连接方式的由异核苷2',5'-脱水-3'-脱氧-3'-(胸腺嘧啶-1-基)-D-甘露糖醇组成的寡核苷酸的杂交特性

Hybrid characteristics of oligonucleotides consisting of isonucleoside 2',5'-anhydro-3'-deoxy-3'-(thymin-1-yl)-D-mannitol with different linkage modes.

作者信息

Lei Z, Zhang L, Zhang L R, Chen J, Min J M, Zhang L H

机构信息

National Research Laboratory of Natural and Biomimetic Drugs, Peking University, 38 Xueyuan Road, Beijing 100083, People's Republic of China.

出版信息

Nucleic Acids Res. 2001 Apr 1;29(7):1470-5. doi: 10.1093/nar/29.7.1470.

DOI:10.1093/nar/29.7.1470
PMID:11266548
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC31276/
Abstract

Oligonucleotides consisting of the isonucleoside repeating unit 2',5'-anhydro-3'-deoxy-3'-(thymin-1-yl)-D-mannitol (4) were synthesized with the monomeric unit 4 incorporated into oligonucleotides as 1'-->4' linkage 4a (oligomer I) or 6'-->4' linkage 4b (oligomer II). The hybrid properties of the two oligonucleotides I and II with their complementary strands were investigated by thermal denaturation and CD spectra. Oligonucleotide I (4a) formed a stable duplex with d(A)(14) with a slightly reduced T(m) value of 36.6 degrees C, relative to 38.2 degrees C for the control duplex d(T)(14)/d(A)(14), but oligomer II (4b) failed to hybridize with a DNA complementary single strand. The spectrum of the duplex oligomer I/d(A)(14) showed a positive CD band at 217 nm and a negative CD band at 248 nm attributable to a B-like conformation. Molecular modeling showed that in the case of oligomer I: the C6' hydroxy group of each unit could be located in the groove area when hybridized to the DNA single strand, which might contribute additional hydrogen bonding to the stability of duplex formation.

摘要

由异核苷重复单元2',5'-脱水-3'-脱氧-3'-(胸腺嘧啶-1-基)-D-甘露糖醇(4)组成的寡核苷酸被合成,其中单体单元4以1'→4'连接4a(低聚物I)或6'→4'连接4b(低聚物II)的形式掺入寡核苷酸中。通过热变性和圆二色光谱研究了两种寡核苷酸I和II与其互补链的杂交特性。寡核苷酸I(4a)与d(A)(14)形成稳定的双链体,相对于对照双链体d(T)(14)/d(A)(14),其熔解温度(Tm)值略有降低,为36.6℃,但低聚物II(4b)未能与DNA互补单链杂交。双链体低聚物I/d(A)(14)的光谱在217nm处显示正的圆二色带,在248nm处显示负的圆二色带,这归因于B样构象。分子建模表明,在低聚物I的情况下:每个单元的C6'羟基在与DNA单链杂交时可位于沟区,这可能为双链体形成的稳定性贡献额外的氢键。

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本文引用的文献

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