Comprehensive and High-Throughput Exploration of Chemical Space Using Broadband 19 Fâ
NMR-Based Screening.
Angew Chem Int Ed Engl
; 59(35): 14809-14817, 2020 08 24.
Article
en En
| MEDLINE
| ID: mdl-32363632
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Tipo de estudio:
Diagnostic_studies
/
Screening_studies
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos