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Systematic Evaluation of On-DNA Nitro Reduction Reactions in Short and Elongated DNA Tags for DNA-Encoded Library
Yeongjoo Suh1,2, Kyung-Jin Cho1, Hyun Jin Kim1,2
1Therapeutics & Biotechnology Division, Korea Research Institute of Chemical Technology, Daejeon34114, Republic of Korea.
Abstract:
DNA-encoded library (DEL) synthesis necessitates robust on-DNA chemical transformations that remain dependable throughout multistep library construction, especially for elongated DNA constructs. This study assessed the efficiency of commonly used on-DNA nitro reduction reactions under conditions relevant to practical DEL synthesis to evaluate the impact of DNA tag elongation. Although iron(II)-, diboron-, palladium(II)-, and dithionite-mediated reductions showed high efficiency for short DNA constructs, their performances varied significantly with DNA tag elongation. The generality of these reduction conditions was further explored across a diverse set of nitro-containing substrates, and their chemoselectivities toward additional functional groups were assessed to reflect realistic DEL design considerations. These findings underscore the importance of evaluating on-DNA chemistry beyond minimal tag systems and offer practical guidance for selecting suitable nitro reduction conditions for reliable DEL construction.
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