Imperial College London
Alternate

ProfessorAlanArmstrong

Faculty of Natural Sciences, Department 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:2020:10.1002/cbic.202000457,
author = {Craven, GB and Affron, DP and Kösel, T and Wong, TLM and Jukes, ZH and Liu, C-T and Morgan, RML and Armstrong, A and Mann, DJ},
doi = {10.1002/cbic.202000457},
journal = {ChemBioChem: a European journal of chemical biology},
pages = {3417--3422},
title = {Multiparameter kinetic analysis for covalent fragment optimization using quantitative irreversible tethering (qIT)},
url = {http://dx.doi.org/10.1002/cbic.202000457},
volume = {21},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Covalent fragments are increasingly being implemented to develop chemical probes but the complex relationship between fragment structure and binding kinetics makes optimization uniquely challenging. We describe a new technique in covalent probe discovery that enables data driven optimization of covalent fragment potency and selectivity. This platform extends beyond the existing methods for covalent fragment hit identification by facilitating rapid multiparameter kinetic analysis of covalent structure-activity relationships through simultaneous determination of Ki, kinact and intrinsic reactivity. We apply this approach to develop novel probes against electrophile sensitive kinases and showcase how multiparameter kinetic analysis enabled a successful fragment merging strategy.
AU  - Craven,GB
AU  - Affron,DP
AU  - Kösel,T
AU  - Wong,TLM
AU  - Jukes,ZH
AU  - Liu,C-T
AU  - Morgan,RML
AU  - Armstrong,A
AU  - Mann,DJ
DO  - 10.1002/cbic.202000457
EP  - 3422
PY  - 2020///
SN  - 1439-4227
SP  - 3417
TI  - Multiparameter kinetic analysis for covalent fragment optimization using quantitative irreversible tethering (qIT)
T2  - ChemBioChem: a European journal of chemical biology
UR  - http://dx.doi.org/10.1002/cbic.202000457
UR  - https://www.ncbi.nlm.nih.gov/pubmed/32659037
UR  - https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cbic.202000457
UR  - http://hdl.handle.net/10044/1/81428
VL  - 21
ER  -
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