Investigations Into Chemically Stabilized Four-Letter DNA for DNA-Encoded Chemistry

DNA-encoded libraries are a prime technology for target-based small molecule screening. Native DNA used as genetic compound barcode is chemically vulnerable under many reaction conditions. DNA barcodes that are composed of pyrimidine nucleobases, 7-deazaadenine, and 7-deaza-8-azaguanine have been in...

Descripción completa

Detalles Bibliográficos
Autores principales: Potowski, Marco, Kunig, Verena B. K., Eberlein, Lukas, Škopić, Mateja Klika, Vakalopoulos, Alexandros, Kast, Stefan M., Brunschweiger, Andreas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Chemistry
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9218945/
https://www.ncbi.nlm.nih.gov/pubmed/35755251
http://dx.doi.org/10.3389/fchem.2022.894563
_version_ 1784732004300881920
author Potowski, Marco
Kunig, Verena B. K.
Eberlein, Lukas
Škopić, Mateja Klika
Vakalopoulos, Alexandros
Kast, Stefan M.
Brunschweiger, Andreas
author_facet Potowski, Marco
Kunig, Verena B. K.
Eberlein, Lukas
Škopić, Mateja Klika
Vakalopoulos, Alexandros
Kast, Stefan M.
Brunschweiger, Andreas
author_sort Potowski, Marco
collection PubMed
description DNA-encoded libraries are a prime technology for target-based small molecule screening. Native DNA used as genetic compound barcode is chemically vulnerable under many reaction conditions. DNA barcodes that are composed of pyrimidine nucleobases, 7-deazaadenine, and 7-deaza-8-azaguanine have been investigated for their suitability for encoded chemistry both experimentally and computationally. These four-letter barcodes were readily ligated by T4 ligation, amplifiable by Taq polymerase, and the resultant amplicons were correctly sequenced. Chemical stability profiling showed a superior chemical stability compared to native DNA, though higher susceptibility to depurination than a three-letter code based on pyrimidine DNA and 7-deazaadenine.
format Online
Article
Text
id pubmed-9218945
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-92189452022-06-24 Investigations Into Chemically Stabilized Four-Letter DNA for DNA-Encoded Chemistry Potowski, Marco Kunig, Verena B. K. Eberlein, Lukas Škopić, Mateja Klika Vakalopoulos, Alexandros Kast, Stefan M. Brunschweiger, Andreas Front Chem Chemistry DNA-encoded libraries are a prime technology for target-based small molecule screening. Native DNA used as genetic compound barcode is chemically vulnerable under many reaction conditions. DNA barcodes that are composed of pyrimidine nucleobases, 7-deazaadenine, and 7-deaza-8-azaguanine have been investigated for their suitability for encoded chemistry both experimentally and computationally. These four-letter barcodes were readily ligated by T4 ligation, amplifiable by Taq polymerase, and the resultant amplicons were correctly sequenced. Chemical stability profiling showed a superior chemical stability compared to native DNA, though higher susceptibility to depurination than a three-letter code based on pyrimidine DNA and 7-deazaadenine. Frontiers Media S.A. 2022-06-09 /pmc/articles/PMC9218945/ /pubmed/35755251 http://dx.doi.org/10.3389/fchem.2022.894563 Text en Copyright © 2022 Potowski, Kunig, Eberlein, Škopić, Vakalopoulos, Kast and Brunschweiger. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Chemistry
Potowski, Marco
Kunig, Verena B. K.
Eberlein, Lukas
Škopić, Mateja Klika
Vakalopoulos, Alexandros
Kast, Stefan M.
Brunschweiger, Andreas
Investigations Into Chemically Stabilized Four-Letter DNA for DNA-Encoded Chemistry
title Investigations Into Chemically Stabilized Four-Letter DNA for DNA-Encoded Chemistry
title_full Investigations Into Chemically Stabilized Four-Letter DNA for DNA-Encoded Chemistry
title_fullStr Investigations Into Chemically Stabilized Four-Letter DNA for DNA-Encoded Chemistry
title_full_unstemmed Investigations Into Chemically Stabilized Four-Letter DNA for DNA-Encoded Chemistry
title_short Investigations Into Chemically Stabilized Four-Letter DNA for DNA-Encoded Chemistry
title_sort investigations into chemically stabilized four-letter dna for dna-encoded chemistry
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9218945/
https://www.ncbi.nlm.nih.gov/pubmed/35755251
http://dx.doi.org/10.3389/fchem.2022.894563
work_keys_str_mv AT potowskimarco investigationsintochemicallystabilizedfourletterdnafordnaencodedchemistry
AT kunigverenabk investigationsintochemicallystabilizedfourletterdnafordnaencodedchemistry
AT eberleinlukas investigationsintochemicallystabilizedfourletterdnafordnaencodedchemistry
AT skopicmatejaklika investigationsintochemicallystabilizedfourletterdnafordnaencodedchemistry
AT vakalopoulosalexandros investigationsintochemicallystabilizedfourletterdnafordnaencodedchemistry
AT kaststefanm investigationsintochemicallystabilizedfourletterdnafordnaencodedchemistry
AT brunschweigerandreas investigationsintochemicallystabilizedfourletterdnafordnaencodedchemistry

Ejemplares similares