In:
Angewandte Chemie, Wiley, Vol. 132, No. 35 ( 2020-08-24), p. 14919-14927
Abstract:
Fragment‐based lead discovery has become a fundamental approach to identify ligands that efficiently interact with disease‐relevant targets. Among the numerous screening techniques, fluorine‐detected NMR has gained popularity owing to its high sensitivity, robustness, and ease of use. To effectively explore chemical space, a universal NMR experiment, a rationally designed fragment library, and a sample composition optimized for a maximal number of compounds and minimal measurement time are required. Here, we introduce a comprehensive method that enabled the efficient assembly of a high‐quality and diverse library containing nearly 4000 fragments and screening for target‐specific binders within days. At the core of the approach is a novel broadband relaxation‐edited NMR experiment that covers the entire chemical shift range of drug‐like 19 F motifs in a single measurement. Our approach facilitates the identification of diverse binders and the fast ligandability assessment of new targets.
Type of Medium:
Online Resource
ISSN:
0044-8249
,
1521-3757
DOI:
10.1002/ange.v132.35
DOI:
10.1002/ange.202002463
Language:
English
Publisher:
Wiley
Publication Date:
2020
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505868-5
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506609-8
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514305-6
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505872-7
detail.hit.zdb_id:
1479266-7
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505867-3
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506259-7
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