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
in 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pyrazoles
/
Quinoxalines
/
Sulfonamides
/
Bridged Bicyclo Compounds, Heterocyclic
/
Photoaffinity Labels
/
Cross-Linking Reagents
/
Vemurafenib
/
Antineoplastic Agents
Type of study:
Diagnostic_studies
/
Screening_studies
Limits:
Humans
Language:
En
Journal:
Angew Chem Int Ed Engl
Year:
2020
Type:
Article
Affiliation country:
United kingdom