Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 58, Issue 28, Pages 9570-9574Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201902513
Keywords
chemical libraries; DNA chemistry; DNA-encoded libraries; Lipinski rules; macrocycles
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Funding
- Swiss National Science Foundation (SNF) [CRSII2_160699]
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Here we show a seven-step chemical synthesis of a DNA-encoded macrocycle library (DEML) on DNA. Inspired by polyketide and mixed peptide-polyketide natural products, the library was designed to incorporate rich backbone diversity. Achieving this diversity, however, comes at the cost of the custom synthesis of bifunctional building block libraries. This study outlines the importance of careful retrosynthetic design in DNA-encoded libraries, while revealing areas where new DNA synthetic methods are needed.
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