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Deliberately losing control of C-H activation processes in the design of small molecule fragment arrays targeting peroxisomal metabolism
journal contribution
posted on 2023-06-07, 07:46 authored by Raysa Khan, Storm Hassell-HartStorm Hassell-Hart, Tobias Krojer, Anthony Bradley, Srikannathasan Velupillai, Romain Talon, Michael Fairhead, Iain Day, Kamlesh Bala, Robert Felix, Paul Kemmitt, Paul Brennan, Frank von Delft, Laura Díaz Sáez, John SpencerJohn Spencer, Kilian HuberCombined photochemical arylation, “nuisance effect” (S N Ar) reaction sequences have been employed in the design of small arrays for immediate deployment in medium throughput X-ray protein-ligand structure determination. Reactions have been deliberately let “out of control,” in terms of selectivity; for example the ortho-arylation of 2-phenylpyridine gave five products resulting from mono-, bis- arylations combined with S N Ar processes. As a result, a number of crystallographic hits against NUDT7, a key peroxisomal CoA ester hydrolase, have been identified.
History
Publication status
- Published
File Version
- Accepted version
Journal
ChemMedChemISSN
1860-7179Publisher
WileyExternal DOI
Event location
GermanyDepartment affiliated with
- Biochemistry Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2020-08-21First Open Access (FOA) Date
2021-08-19First Compliant Deposit (FCD) Date
2020-08-21Usage metrics
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