A Photoaffinity-Based Fragment-Screening Platform for Efficient Identification of Protein Ligands
Emma K. Grant
GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY UK
Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow, G1 1XL UK
Search for more papers by this authorDavid J. Fallon
GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY UK
Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow, G1 1XL UK
Search for more papers by this authorMichael M. Hann
GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY UK
Search for more papers by this authorKen G. M. Fantom
GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY UK
Search for more papers by this authorChad Quinn
GlaxoSmithKline, South Collegeville Road, Collegeville, PA, 19426 USA
Search for more papers by this authorFrancesca Zappacosta
GlaxoSmithKline, South Collegeville Road, Collegeville, PA, 19426 USA
Search for more papers by this authorRoland S. Annan
GlaxoSmithKline, South Collegeville Road, Collegeville, PA, 19426 USA
Search for more papers by this authorChun-wa Chung
GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY UK
Search for more papers by this authorPaul Bamborough
GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY UK
Search for more papers by this authorDavid P. Dixon
GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY UK
Search for more papers by this authorPeter Stacey
GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY UK
Search for more papers by this authorDavid House
GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY UK
Search for more papers by this authorVipulkumar K. Patel
GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY UK
Search for more papers by this authorNicholas C. O. Tomkinson
Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow, G1 1XL UK
Search for more papers by this authorCorresponding Author
Jacob T. Bush
GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY UK
Search for more papers by this authorEmma K. Grant
GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY UK
Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow, G1 1XL UK
Search for more papers by this authorDavid J. Fallon
GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY UK
Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow, G1 1XL UK
Search for more papers by this authorMichael M. Hann
GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY UK
Search for more papers by this authorKen G. M. Fantom
GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY UK
Search for more papers by this authorChad Quinn
GlaxoSmithKline, South Collegeville Road, Collegeville, PA, 19426 USA
Search for more papers by this authorFrancesca Zappacosta
GlaxoSmithKline, South Collegeville Road, Collegeville, PA, 19426 USA
Search for more papers by this authorRoland S. Annan
GlaxoSmithKline, South Collegeville Road, Collegeville, PA, 19426 USA
Search for more papers by this authorChun-wa Chung
GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY UK
Search for more papers by this authorPaul Bamborough
GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY UK
Search for more papers by this authorDavid P. Dixon
GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY UK
Search for more papers by this authorPeter Stacey
GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY UK
Search for more papers by this authorDavid House
GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY UK
Search for more papers by this authorVipulkumar K. Patel
GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY UK
Search for more papers by this authorNicholas C. O. Tomkinson
Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow, G1 1XL UK
Search for more papers by this authorCorresponding Author
Jacob T. Bush
GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY UK
Search for more papers by this authorAbstract
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.
Conflict of interest
The authors declare no conflict of interest.
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