Considerations for Achieving Maximized DNA Recovery in Solid-Phase DNA-Encoded Library Synthesis.

ABSTRACT: DNA-encoded library (DEL) technology enables rapid, economical synthesis, and exploration of novel chemical space. Reaction development for DEL synthesis has recently accelerated in pace with a specific emphasis on ensuring that the reaction does not compromise the integrity of the encoding DNA. However, the factors that contribute to a reaction's "DNA compatibility" remain relatively unknown. We investigated several solid-phase reactions and encoding conditions and determined their impact on DNA compatibility. Conditions that minimized the accessibility of reactive groups on the DNA encoding tag (switching solvent, low temperature, double-stranded encoding tag) significantly improved compatibility. We showcased this approach in the multistep synthesis of an acyldepsipeptide (ADEP1) fragme

SUBMITTER: Price AK 

PROVIDER: S-EPMC7655546 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature