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

Epple, Sven; Modi, Aman; Baker, Ysobel R.; Wegrzyn, Ewa; Traore, Diallo; Wanat, Przemyslaw; Tyburn, Agnes E. S.; Shivalingam, Arun; Taemaitree, Lapatrada; El-Sagheer, Afaf H. und Brown, Tom (2021): A New 1,5-Disubstituted Triazole DNA Backbone Mimic with Enhanced Polymerase Compatibility. In: Journal of the American Chemical Society, Bd. 143, Nr. 39: S. 16293-16301

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Chemie und Pharmazie > Department Chemie
• Themengebiete: 500 Naturwissenschaften und Mathematik > 540 Chemie
• ISSN: 0002-7863
• Sprache: Englisch