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

J Am Chem Soc. 2021 Oct 6;143(39):16293-16301. doi: 10.1021/jacs.1c08057. Epub 2021 Sep 21.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalysis
  • DNA / chemistry*
  • DNA-Directed DNA Polymerase / metabolism*
  • Dinucleoside Phosphates / chemistry
  • Molecular Mimicry
  • Triazoles / chemistry*

Substances

  • Dinucleoside Phosphates
  • Triazoles
  • DNA
  • DNA-Directed DNA Polymerase