A Novel NMR-Based Protocol to Screen Ultralow Molecular Weight Fragments.
J Med Chem
; 67(5): 3874-3884, 2024 Mar 14.
Article
en En
| MEDLINE
| ID: mdl-38426508
ABSTRACT
Fragment-based lead discovery has emerged as one of the most efficient screening strategies for finding hit molecules in drug discovery. Recently, a novel strategy based on a class of fragments characterized by an ultralow molecular weight (ULMW) has been proposed. These fragments bind to the target with a very low affinity, requiring reliable biophysical methods for detection. The most notable application of ULMW used a set of 81 fragments, named MiniFrags, and screened them by X-ray crystallography. We extended the utilization of this novel class of fragments to another gold standard technique for fragment-based screening nuclear magnetic resonance (NMR). Here, we present a novel NMR protocol to detect and analyze such weak interactions in a challenging real-world scenario a flexible target with a flat, water-exposed binding site. We identified a subset of 69 highly water-soluble MiniFrags that were screened against the antiapoptotic protein human Bfl-1.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Bibliotecas de Moléculas Pequeñas
/
Descubrimiento de Drogas
Límite:
Humans
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Italia