Stress Cedric J, Sauter Basilius, Schneider Lukas A, Sharpe Timothy, Gillingham Dennis
Department of Chemistry, University of Basel, St. Johanns-Ring 19, CH-4056, Basel, Switzerland.
Biophysics Facility, Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056, Basel, Switzerland.
Angew Chem Int Ed Engl. 2019 Jul 8;58(28):9570-9574. doi: 10.1002/anie.201902513. Epub 2019 Jun 6.
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.
在此，我们展示了一种在DNA上进行的七步化学合成DNA编码大环化合物库（DEML）的方法。受聚酮化合物以及混合肽 - 聚酮化合物天然产物的启发，该文库旨在纳入丰富的骨架多样性。然而，要实现这种多样性，需要以定制合成双功能构建体文库为代价。本研究概述了在DNA编码文库中进行仔细的逆合成设计的重要性，同时揭示了需要新的DNA合成方法的领域。
