A DNA-Encoded Chemical Library Incorporating Elements of Natural Macrocycles

被引：71
作者：
Stress, Cedric J. [1 ]
Sauter, Basilius [1 ]
Schneider, Lukas A. [1 ]
Sharpe, Timothy [2 ]
Gillingham, Dennis [1 ]
机构：
[1] Univ Basel, Dept Chem, St Johanns Ring 19, CH-4056 Basel, Switzerland
[2] Univ Basel, Biozentrum, Biophys Facil, Klingelbergstr 50-70, CH-4056 Basel, Switzerland
来源：
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2019年 / 58卷 / 28期
基金：
瑞士国家科学基金会;
关键词：
chemical libraries; DNA chemistry; DNA-encoded libraries; Lipinski rules; macrocycles; DRUG DISCOVERY; TEMPLATED SYNTHESIS; SELECTION; BINDING; PERMEABILITY; SOLUBILITY; DISPLAY; DESIGN;
D O I：
10.1002/anie.201902513
中图分类号：
O6 [化学];
学科分类号：
0703 ;
摘要：
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.
引用
收藏
页码：9570 / 9574
页数：5
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