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...

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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
Descripción
Sumario: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.

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