Imperial College London

ProfessorAlanArmstrong

Faculty of Natural SciencesDepartment of Chemistry

Professor of Organic Synthesis
 
 
 
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Contact

 

+44 (0)20 7594 5876a.armstrong

 
 
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Location

 

501EMolecular Sciences Research HubWhite City Campus

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Summary

 

Publications

Citation

BibTex format

@article{Craven:2018:10.1002/anie.201711825,
author = {Craven, G and Affron, D and Allen, C and Matthies, S and Greener, J and Morgan, R and Tate, E and Armstrong, A and Mann, D},
doi = {10.1002/anie.201711825},
journal = {Angewandte Chemie},
pages = {5257--5261},
title = {High-throughput kinetic analysis for target-directed covalent ligand discovery},
url = {http://dx.doi.org/10.1002/anie.201711825},
volume = {57},
year = {2018}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Cysteine-­reactive small molecules are used as chemical probes of biological systems and as medicines. Identifying high-­quality covalent ligands requires comprehensive kinetic analysis to distinguish selective binders from pan-­reactive compounds. Here we describe quantitative irreversible tethering(qIT), a general method for screening cysteine-­reactive small moleculesbased upon the maximization of kinetic selectivity. We apply this method prospectively to discover covalent fragments that target the clinically important cell cycle regulator Cdk2. Crystal structures of the inhibitor complexes validate the approach and guide further optimization. The power of this technique is highlighted by the identification of a Cdk2-­selective allosteric (type IV) kinase inhibitor whose novel mode-­of-­action could be exploited therapeutically.
AU - Craven,G
AU - Affron,D
AU - Allen,C
AU - Matthies,S
AU - Greener,J
AU - Morgan,R
AU - Tate,E
AU - Armstrong,A
AU - Mann,D
DO - 10.1002/anie.201711825
EP - 5261
PY - 2018///
SN - 1521-3757
SP - 5257
TI - High-throughput kinetic analysis for target-directed covalent ligand discovery
T2 - Angewandte Chemie
UR - http://dx.doi.org/10.1002/anie.201711825
UR - http://hdl.handle.net/10044/1/57267
VL - 57
ER -