NMR quality control of fragment libraries for screening.
J Biomol NMR
; 74(10-11): 555-563, 2020 Nov.
Article
en En
| MEDLINE
| ID: mdl-32533387
ABSTRACT
Fragment-based screening has evolved as a remarkable approach within the drug discovery process both in the industry and academia. Fragment screening has become a more structure-based approach to inhibitor development, but also towards development of pathway-specific clinical probes. However, it is often witnessed that the availability, immediate and long-term, of a high quality fragment-screening library is still beyond the reach of most academic laboratories. Within iNEXT (Infrastructure for NMR, EM and X-rays for Translational research), a EU-funded Horizon 2020 program, a collection of 782 fragments were assembled utilizing the concept of "poised fragments" with the aim to facilitate downstream synthesis of ligands with high affinity by fragment ligation. Herein, we describe the analytical procedure to assess the quality of this purchased and assembled fragment library by NMR spectroscopy. This quality assessment requires buffer solubility screening, comparison with LC/MS quality control and is supported by state-of-the-art software for high throughput data acquisition and on-the-fly data analysis. Results from the analysis of the library are presented as a prototype of fragment progression through the quality control process.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Resonancia Magnética Nuclear Biomolecular
/
Bibliotecas de Moléculas Pequeñas
/
Descubrimiento de Drogas
Tipo de estudio:
Diagnostic_studies
/
Screening_studies
Idioma:
En
Revista:
J Biomol NMR
Asunto de la revista:
BIOLOGIA MOLECULAR
/
DIAGNOSTICO POR IMAGEM
/
MEDICINA NUCLEAR
Año:
2020
Tipo del documento:
Article
País de afiliación:
Alemania