AUTHOR=Potowski Marco , Kunig Verena B. K. , Eberlein Lukas , Škopić Mateja Klika , Vakalopoulos Alexandros , Kast Stefan M. , Brunschweiger Andreas TITLE=Investigations Into Chemically Stabilized Four-Letter DNA for DNA-Encoded Chemistry JOURNAL=Frontiers in Chemistry VOLUME=10 YEAR=2022 URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2022.894563 DOI=10.3389/fchem.2022.894563 ISSN=2296-2646 ABSTRACT=

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.