A Photoaffinity-Based Fragment-Screening Platform for Efficient Identification of Protein Ligands.
Angew Chem Int Ed Engl
; 59(47): 21096-21105, 2020 11 16.
Article
em En
| MEDLINE
| ID: mdl-32745361
ABSTRACT
Advances in genomic analyses enable the identification of new proteins that are associated with disease. To validate these targets, tool molecules are required to demonstrate that a ligand can have a disease-modifying effect. Currently, as tools are reported for only a fraction of the proteome, platforms for ligand discovery are essential to leverage insights from genomic analyses. Fragment screening offers an efficient approach to explore chemical space. Presented here is a fragment-screening platform, termed PhABits (PhotoAffinity Bits), which utilizes a library of photoreactive fragments to covalently capture fragment-protein interactions. Hits can be profiled to determine potency and the site of crosslinking, and subsequently developed as reporters in a competitive displacement assay to identify novel hit matter. The PhABit platform is envisioned to be widely applicable to novel protein targets, identifying starting points in the development of therapeutics.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirazóis
/
Quinoxalinas
/
Sulfonamidas
/
Compostos Bicíclicos Heterocíclicos com Pontes
/
Marcadores de Fotoafinidade
/
Reagentes de Ligações Cruzadas
/
Vemurafenib
/
Antineoplásicos
Tipo de estudo:
Diagnostic_studies
/
Screening_studies
Limite:
Humans
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Reino Unido