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

[Image: see text] 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 incorpora...

Descripción completa

Detalles Bibliográficos
Autores principales: Epple, Sven, Modi, Aman, Baker, Ysobel R., Wȩgrzyn, Ewa, Traoré, Diallo, Wanat, Przemyslaw, Tyburn, Agnes E. S., Shivalingam, Arun, Taemaitree, Lapatrada, El-Sagheer, Afaf H., Brown, Tom
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2021
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8499026/
https://www.ncbi.nlm.nih.gov/pubmed/34546729
http://dx.doi.org/10.1021/jacs.1c08057
_version_ 1784580290256044032
author Epple, Sven
Modi, Aman
Baker, Ysobel R.
Wȩgrzyn, Ewa
Traoré, Diallo
Wanat, Przemyslaw
Tyburn, Agnes E. S.
Shivalingam, Arun
Taemaitree, Lapatrada
El-Sagheer, Afaf H.
Brown, Tom
author_facet Epple, Sven
Modi, Aman
Baker, Ysobel R.
Wȩgrzyn, Ewa
Traoré, Diallo
Wanat, Przemyslaw
Tyburn, Agnes E. S.
Shivalingam, Arun
Taemaitree, Lapatrada
El-Sagheer, Afaf H.
Brown, Tom
author_sort Epple, Sven
collection PubMed
description [Image: see text] 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.
format Online
Article
Text
id pubmed-8499026
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher American Chemical Society
record_format MEDLINE/PubMed
spelling pubmed-84990262021-10-12 A New 1,5-Disubstituted Triazole DNA Backbone Mimic with Enhanced Polymerase Compatibility Epple, Sven Modi, Aman Baker, Ysobel R. Wȩgrzyn, Ewa Traoré, Diallo Wanat, Przemyslaw Tyburn, Agnes E. S. Shivalingam, Arun Taemaitree, Lapatrada El-Sagheer, Afaf H. Brown, Tom J Am Chem Soc [Image: see text] 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. American Chemical Society 2021-09-21 2021-10-06 /pmc/articles/PMC8499026/ /pubmed/34546729 http://dx.doi.org/10.1021/jacs.1c08057 Text en © 2021 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Epple, Sven
Modi, Aman
Baker, Ysobel R.
Wȩgrzyn, Ewa
Traoré, Diallo
Wanat, Przemyslaw
Tyburn, Agnes E. S.
Shivalingam, Arun
Taemaitree, Lapatrada
El-Sagheer, Afaf H.
Brown, Tom
A New 1,5-Disubstituted Triazole DNA Backbone Mimic with Enhanced Polymerase Compatibility
title A New 1,5-Disubstituted Triazole DNA Backbone Mimic with Enhanced Polymerase Compatibility
title_full A New 1,5-Disubstituted Triazole DNA Backbone Mimic with Enhanced Polymerase Compatibility
title_fullStr A New 1,5-Disubstituted Triazole DNA Backbone Mimic with Enhanced Polymerase Compatibility
title_full_unstemmed A New 1,5-Disubstituted Triazole DNA Backbone Mimic with Enhanced Polymerase Compatibility
title_short A New 1,5-Disubstituted Triazole DNA Backbone Mimic with Enhanced Polymerase Compatibility
title_sort new 1,5-disubstituted triazole dna backbone mimic with enhanced polymerase compatibility
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8499026/
https://www.ncbi.nlm.nih.gov/pubmed/34546729
http://dx.doi.org/10.1021/jacs.1c08057
work_keys_str_mv AT epplesven anew15disubstitutedtriazolednabackbonemimicwithenhancedpolymerasecompatibility
AT modiaman anew15disubstitutedtriazolednabackbonemimicwithenhancedpolymerasecompatibility
AT bakerysobelr anew15disubstitutedtriazolednabackbonemimicwithenhancedpolymerasecompatibility
AT wegrzynewa anew15disubstitutedtriazolednabackbonemimicwithenhancedpolymerasecompatibility
AT traorediallo anew15disubstitutedtriazolednabackbonemimicwithenhancedpolymerasecompatibility
AT wanatprzemyslaw anew15disubstitutedtriazolednabackbonemimicwithenhancedpolymerasecompatibility
AT tyburnagneses anew15disubstitutedtriazolednabackbonemimicwithenhancedpolymerasecompatibility
AT shivalingamarun anew15disubstitutedtriazolednabackbonemimicwithenhancedpolymerasecompatibility
AT taemaitreelapatrada anew15disubstitutedtriazolednabackbonemimicwithenhancedpolymerasecompatibility
AT elsagheerafafh anew15disubstitutedtriazolednabackbonemimicwithenhancedpolymerasecompatibility
AT browntom anew15disubstitutedtriazolednabackbonemimicwithenhancedpolymerasecompatibility
AT epplesven new15disubstitutedtriazolednabackbonemimicwithenhancedpolymerasecompatibility
AT modiaman new15disubstitutedtriazolednabackbonemimicwithenhancedpolymerasecompatibility
AT bakerysobelr new15disubstitutedtriazolednabackbonemimicwithenhancedpolymerasecompatibility
AT wegrzynewa new15disubstitutedtriazolednabackbonemimicwithenhancedpolymerasecompatibility
AT traorediallo new15disubstitutedtriazolednabackbonemimicwithenhancedpolymerasecompatibility
AT wanatprzemyslaw new15disubstitutedtriazolednabackbonemimicwithenhancedpolymerasecompatibility
AT tyburnagneses new15disubstitutedtriazolednabackbonemimicwithenhancedpolymerasecompatibility
AT shivalingamarun new15disubstitutedtriazolednabackbonemimicwithenhancedpolymerasecompatibility
AT taemaitreelapatrada new15disubstitutedtriazolednabackbonemimicwithenhancedpolymerasecompatibility
AT elsagheerafafh new15disubstitutedtriazolednabackbonemimicwithenhancedpolymerasecompatibility
AT browntom new15disubstitutedtriazolednabackbonemimicwithenhancedpolymerasecompatibility

Ejemplares similares