Resistance towards exonucleases of dinucleotides with stereochemically altered internucleotide phosphate bonds.

Resistance towards exonucleases of dinucleotides with stereochemically altered internucleotide phosphate bonds.
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对具有立体化学改变的核苷酸间磷酸键的二核苷酸核酸外切酶的抗性。

DOI:
10.1016/j.bmcl.2003.07.034
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发表时间:
2004
影响因子:
2.7
通讯作者:
Pal,Suresh
Pal,Suresh
中科院分区:
医学4区
文献类型:
--
作者:
Nair,Vasu;Pal,Suresh

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正常二核苷酸中核苷酸间磷酸键水解敏感性的动力学常数[例如,2′-脱氧胞苷酰-(3′ → 5′)-2′-脱氧尿苷(dCpdU)和2′-脱氧腺苷酰-(3′→5′)-2′-脱氧胞苷(dApdC)]和异构二核苷酸[例如,2′-脱氧胞苷酰-(3′→5′)-1′-脱氧-2 ′-异尿苷(dCpisodU)和1′-脱氧-2 ′-异腺苷酰-(3′→5′)-2′-脱氧胞苷(isodApdC)]对5′-和3′-外切核酸酶磷酸二酯酶Ⅰ(PDE Ⅰ)和磷酸二酯酶Ⅱ(PDE Ⅱ)的反应,实验结果显示有显著差异。这项研究在发现HIV整合酶的核酸酶稳定抑制剂方面具有重要意义,但也可能在具有治疗意义的反义寡核苷酸领域产生影响。
Kinetic constants for the hydrolytic susceptibility of the internucleotide phosphate bond in normal dinucleotides [e.g., 2′-deoxycytidylyl-(3′>5′)-2′-deoxyuridine (dCpdU) and 2′-deoxyadenylyl-(3′→5′)-2′-deoxycytidine (dApdC)] and isomeric dinucleotides [e.g., 2′-deoxycytidylyl-(3′→5′)-1′-deoxy-2′-isouridine (dCpisodU) and 1′-deoxy-2′-isoadenylyl-(3′→5′)-2′-deoxycytidine (isodApdC)], toward 5′- and 3′-exonucleases, phosphodiesterase I (PDE I) and phosphodiesterase II (PDE II) were experimentally determined and remarkable differences emerged. The study is of importance in the discovery of nuclease-stable inhibitors of HIV integrase, but may also have ramifications in the area of anti-sense oligonucleotides of therapeutic interest.
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