Chemistry Research Laboratory, University of Oxford, Oxford, OX1 3TA, U.K.
Chemistry Branch, Department of Science and Mathematics, Faculty of Petroleum and Mining Engineering, Suez University, Suez 43721, Egypt.
J Am Chem Soc. 2021 Oct 6;143(39):16293-16301. doi: 10.1021/jacs.1c08057. Epub 2021 Sep 21.
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 (TL) dinucleoside phosphoramidite as well as its incorporation into oligonucleotides and compare its DNA polymerase replication competency with other TL analogues. We demonstrate that TL 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.
三唑键（TLs）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有广泛的应用。在这里，我们报告了 RuAAC 催化合成一种新型 1,5-取代三唑（TL）二核苷亚磷酰胺，并将其掺入寡核苷酸中，并与其他 TL 类似物进行比较其 DNA 聚合酶复制能力。我们证明 TL 的复制动力学优于这些类似物，并且被聚合酶准确复制。衍生的结构-生物相容性关系表明，连接体长度和氢键受体的取向是关键的，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。
