Unknown

Dataset Information

0

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) fragment, which preserved 73% of DNA for a >100-fold improvement over canonical conditions. These results are particularly encouraging in the context of multistep reaction sequences to access natural product-like scaffolds and more broadly underscore the importance of reconciling the biophysical properties and reactivity of DNA with chemistry development to yield high-quality libraries of those scaffolds.

SUBMITTER: Price AK 

PROVIDER: S-EPMC7655546 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC4571006 | biostudies-other
| S-EPMC7298663 | biostudies-literature
| S-EPMC6938256 | biostudies-literature
| S-EPMC2532789 | biostudies-literature
| S-EPMC6393171 | biostudies-literature
| S-EPMC9285660 | biostudies-literature
| S-EPMC6957756 | biostudies-literature
| S-EPMC6706801 | biostudies-literature
| S-EPMC7294439 | biostudies-literature
| S-EPMC7060506 | biostudies-literature