In:
Angewandte Chemie International Edition, Wiley, Vol. 58, No. 27 ( 2019-07), p. 9254-9261
Abstract:
DNA encoded chemical libraries (DELs) link the powers of genetics and chemical synthesis via combinatorial optimization. Through combinatorial chemistry, DELs can grow to the unprecedented size of billions to trillions. To take full advantage of the DEL approach, linking the power of genetics directly to chemical structures would offer even greater diversity in a finite chemical world. Natural products have evolved an incredible structural diversity along with their biological evolution. Herein, we used traditional Chinese medicines (TCMs) as examples in a late‐stage modification toolbox approach to annotate these complex organic compounds with amplifiable DNA barcodes, which could be easily incorporated into a DEL. The method of end‐products labeling also generates a cluster of isomers with a single DNA tag at different sites. These isomers provide an additional spatial diversity for multiple accessible pockets of targeted proteins. Notably, a novel PARP1 inhibitor from TCM has been identified from the natural products enriched DEL ( n DEL).
Type of Medium:
Online Resource
ISSN:
1433-7851
,
1521-3773
DOI:
10.1002/anie.201901485
Language:
English
Publisher:
Wiley
Publication Date:
2019
detail.hit.zdb_id:
2011836-3
detail.hit.zdb_id:
123227-7
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