>>Ligand and Target Discovery by Fragment-Based Screening in Human Cells
Christopher G. Parker5, Correspondence information about the author Christopher G. Parker  Email the author Christopher G. Parker
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Andrea Galmozzi5
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Yujia Wang
,
Bruno E. Correia
,
Kenji Sasaki
,
Christopher M. Joslyn
,
Arthur S. Kim
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Cullen L. Cavallaro
,
R. Michael Lawrence
,
Stephen R. Johnson
,
Iñigo Narvaiza
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Enrique SaezCorrespondence information about the author Enrique Saez Email the author Enrique Saez
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Benjamin F. Cravatt6,Correspondence information about the author Benjamin F. Cravatt Email the author Benjamin F. Cravatt
5Co-first author
6Lead Contact
DOI: dx.doi.org
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 Article Info
Publication History
Published: January 19, 2017Accepted: December 20, 2016Received in revised form: November 14, 2016Received: September 12, 2016
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Highlights
•Chemical proteomics identifies numerous fragment-protein interactions in cells•Interactions can be advanced into selective ligands that modulate protein function•Fragment-based probes facilitate target identification in phenotypic screening•Fragment-based ligands promote adipogenesis by stimulating PGRMC2 function
Summary
Advances in the synthesis and screening of small-molecule libraries have accelerated the discovery of chemical probes for studying biological processes. Still, only a small fraction of the human proteome has chemical ligands. Here, we describe a platform that marries fragment-based ligand discovery with quantitative chemical proteomics to map thousands of reversible small molecule-protein interactions directly in human cells, many of which can be site-specifically determined. We show that fragment hits can be advanced to furnish selective ligands that affect the activity of proteins heretofore lacking chemical probes. We further combine fragment-based chemical proteomics with phenotypic screening to identify small molecules that promote adipocyte differentiation by engaging the poorly characterized membrane protein PGRMC2. Fragment-based screening in human cells thus provides an extensive proteome-wide map of protein ligandability and facilitates the coordinated discovery of bioactive small molecules and their molecular targets.<<
Wow! Almost a decade since anyone posted here. But proteomics isn't dead, it's just evolving. The author include Bristol Myers personnel. I have no idea what the IP/licensing situation is. This appears to be a non-obvious improvement on existing technique, to me (who knows little). Should provide some help for the early stage pipe of whoever is allowed to use it.
Cheers, Tuck |
