Overcoming the Limitations of Fragment Merging: Rescuing a Strained Merged Fragment Series Targeting Mycobacterium tuberculosis CYP121

Freedom to merge: A combination of crystal structure examination and in silico predictions made it possible to overcome the conformational limitations of fragment merging and escape the internal strain in a series of weakly binding merged fragments that target M. tuberculosis CYP121. The insights at...

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Detalles Bibliográficos
Autores principales: Hudson, Sean A., Surade, Sachin, Coyne, Anthony G., McLean, Kirsty J., Leys, David, Munro, Andrew W., Abell, Chris
Formato: Online Artículo Texto
Lenguaje:English
Publicado: WILEY‐VCH Verlag 2013
Materias:
Communications
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4281926/
https://www.ncbi.nlm.nih.gov/pubmed/23788280
http://dx.doi.org/10.1002/cmdc.201300219
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author Hudson, Sean A.
Surade, Sachin
Coyne, Anthony G.
McLean, Kirsty J.
Leys, David
Munro, Andrew W.
Abell, Chris
author_facet Hudson, Sean A.
Surade, Sachin
Coyne, Anthony G.
McLean, Kirsty J.
Leys, David
Munro, Andrew W.
Abell, Chris
author_sort Hudson, Sean A.
collection PubMed
description Freedom to merge: A combination of crystal structure examination and in silico predictions made it possible to overcome the conformational limitations of fragment merging and escape the internal strain in a series of weakly binding merged fragments that target M. tuberculosis CYP121. The insights attained provide a new perspective and guide for prioritizing synthetic efforts toward fragment merging in future and ongoing fragment‐based ligand discovery campaigns.[Image: see text]
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spelling pubmed-42819262015-01-15 Overcoming the Limitations of Fragment Merging: Rescuing a Strained Merged Fragment Series Targeting Mycobacterium tuberculosis CYP121 Hudson, Sean A. Surade, Sachin Coyne, Anthony G. McLean, Kirsty J. Leys, David Munro, Andrew W. Abell, Chris ChemMedChem Communications Freedom to merge: A combination of crystal structure examination and in silico predictions made it possible to overcome the conformational limitations of fragment merging and escape the internal strain in a series of weakly binding merged fragments that target M. tuberculosis CYP121. The insights attained provide a new perspective and guide for prioritizing synthetic efforts toward fragment merging in future and ongoing fragment‐based ligand discovery campaigns.[Image: see text] WILEY‐VCH Verlag 2013-08-27 2013-06-20 /pmc/articles/PMC4281926/ /pubmed/23788280 http://dx.doi.org/10.1002/cmdc.201300219 Text en © 2013 The Authors. Published by Wiley‐VCH Verlag GmbH & Co. KGaA. https://creativecommons.org/licenses/by/4.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Communications
Hudson, Sean A.
Surade, Sachin
Coyne, Anthony G.
McLean, Kirsty J.
Leys, David
Munro, Andrew W.
Abell, Chris
Overcoming the Limitations of Fragment Merging: Rescuing a Strained Merged Fragment Series Targeting Mycobacterium tuberculosis CYP121
title Overcoming the Limitations of Fragment Merging: Rescuing a Strained Merged Fragment Series Targeting Mycobacterium tuberculosis CYP121
title_full Overcoming the Limitations of Fragment Merging: Rescuing a Strained Merged Fragment Series Targeting Mycobacterium tuberculosis CYP121
title_fullStr Overcoming the Limitations of Fragment Merging: Rescuing a Strained Merged Fragment Series Targeting Mycobacterium tuberculosis CYP121
title_full_unstemmed Overcoming the Limitations of Fragment Merging: Rescuing a Strained Merged Fragment Series Targeting Mycobacterium tuberculosis CYP121
title_short Overcoming the Limitations of Fragment Merging: Rescuing a Strained Merged Fragment Series Targeting Mycobacterium tuberculosis CYP121
title_sort overcoming the limitations of fragment merging: rescuing a strained merged fragment series targeting mycobacterium tuberculosis cyp121
topic Communications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4281926/
https://www.ncbi.nlm.nih.gov/pubmed/23788280
http://dx.doi.org/10.1002/cmdc.201300219
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