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

Autor: Epple S; Chemistry Research Laboratory, University of Oxford, Oxford, OX1 3TA, U.K., Modi A; Chemistry Research Laboratory, University of Oxford, Oxford, OX1 3TA, U.K., Baker YR; Chemistry Research Laboratory, University of Oxford, Oxford, OX1 3TA, U.K., Wȩgrzyn E; Chemistry Research Laboratory, University of Oxford, Oxford, OX1 3TA, U.K., Traoré D; Chemistry Research Laboratory, University of Oxford, Oxford, OX1 3TA, U.K., Wanat P; Chemistry Research Laboratory, University of Oxford, Oxford, OX1 3TA, U.K., Tyburn AES; Chemistry Research Laboratory, University of Oxford, Oxford, OX1 3TA, U.K., Shivalingam A; Chemistry Research Laboratory, University of Oxford, Oxford, OX1 3TA, U.K., Taemaitree L; Chemistry Research Laboratory, University of Oxford, Oxford, OX1 3TA, U.K., El-Sagheer AH; 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., Brown T; Chemistry Research Laboratory, University of Oxford, Oxford, OX1 3TA, U.K.
Jazyk: angličtina
Zdroj: Journal of the American Chemical Society [J Am Chem Soc] 2021 Oct 06; Vol. 143 (39), pp. 16293-16301. Date of Electronic Publication: 2021 Sep 21.
DOI: 10.1021/jacs.1c08057
Abstrakt: 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 2 ) dinucleoside phosphoramidite as well as its incorporation into oligonucleotides and compare its DNA polymerase replication competency with other TL analogues. We demonstrate that TL 2 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.
Databáze: MEDLINE
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