A New 1,5-Disubstituted Triazole DNA Backbone Mimic with Enhanced Polymerase Compatibility.

A New 1,5-Disubstituted Triazole DNA Backbone Mimic with Enhanced Polymerase Compatibility.
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具有增强聚合酶相容性的新型1,5-二取代三唑DNA主链模拟物。

DOI:
10.1021/jacs.1c08057
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发表时间:
2021-10-06
影响因子:
15
通讯作者:
Brown T
Brown T
中科院分区:
化学1区
文献类型:
--
作者:
Epple S;Modi A;Baker YR;Wȩgrzyn E;Traoré D;Wanat P;Tyburn AES;Shivalingam A;Taemaitree L;El-Sagheer AH;Brown T

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三唑键(TL)是寡核苷酸中磷酸二酯键的模拟物,在合成生物学和生物技术中具有应用。在这里,我们报告的RuAAC催化合成的一种新的1,5-二取代三唑(TL 2)二核苷亚磷酰胺,以及其纳入寡核苷酸和比较其DNA聚合酶的复制能力与其他TL类似物。我们证明TL 2具有优于这些类似物的上级复制动力学,并且可以通过聚合酶准确复制。衍生的结构-生物相容性关系表明,连接体的长度和氢键受体的方向是至关重要的,并为人工生物相容性核酸骨架的合理设计提供了进一步的指导。
Triazole linkages (TLs) are mimics of the phosphodiester bond in oligonucleotides with applications in synthetic biology and biotechnology. Here we report the RuAAC-catalyzed synthesis of a novel 1,5-disubstituted triazole (TL2) dinucleoside phosphoramidite as well as its incorporation into oligonucleotides and compare its DNA polymerase replication competency with other TL analogues. We demonstrate that TL2 has superior replication kinetics to these analogues and is accurately replicated by polymerases. Derived structure–biocompatibility relationships show that linker length and the orientation of a hydrogen bond acceptor are critical and provide further guidance for the rational design of artificial biocompatible nucleic acid backbones.
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