| Autor: |
Price AK; Department of Chemistry Scripps Research 130 Scripps Way, Jupiter, Florida 33458, United States., Paegel BM; Department of Chemistry Scripps Research 130 Scripps Way, Jupiter, Florida 33458, United States. |
| Jazyk: |
angličtina |
| Zdroj: |
ACS combinatorial science [ACS Comb Sci] 2020 Nov 09; Vol. 22 (11), pp. 649-655. Date of Electronic Publication: 2020 Aug 24. |
| DOI: |
10.1021/acscombsci.0c00101 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
