A Proof-of-Concept Fragment Screening of a Hit-Validated 96-Compounds Library against Human Carbonic Anhydrase II

Fragment screening is a powerful tool to identify and characterize binding pockets in proteins. We herein present the results of a proof-of-concept screening campaign of a versatile 96-entry fragment library from our laboratory against the drug target and model protein human carbonic anhydrase II. T...

Descripción completa

Detalles Bibliográficos
Autores principales: Glöckner, Steffen, Heine, Andreas, Klebe, Gerhard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226012/
https://www.ncbi.nlm.nih.gov/pubmed/32235320
http://dx.doi.org/10.3390/biom10040518
_version_ 1783534187789156352
author Glöckner, Steffen
Heine, Andreas
Klebe, Gerhard
author_facet Glöckner, Steffen
Heine, Andreas
Klebe, Gerhard
author_sort Glöckner, Steffen
collection PubMed
description Fragment screening is a powerful tool to identify and characterize binding pockets in proteins. We herein present the results of a proof-of-concept screening campaign of a versatile 96-entry fragment library from our laboratory against the drug target and model protein human carbonic anhydrase II. The screening revealed a novel chemotype for carbonic anhydrase inhibition, as well as less common non-covalent interaction types and unexpected covalent linkages. Lastly, different runs of the PanDDA tool reveal a practical hint for its application.
format Online
Article
Text
id pubmed-7226012
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-72260122020-05-18 A Proof-of-Concept Fragment Screening of a Hit-Validated 96-Compounds Library against Human Carbonic Anhydrase II Glöckner, Steffen Heine, Andreas Klebe, Gerhard Biomolecules Article Fragment screening is a powerful tool to identify and characterize binding pockets in proteins. We herein present the results of a proof-of-concept screening campaign of a versatile 96-entry fragment library from our laboratory against the drug target and model protein human carbonic anhydrase II. The screening revealed a novel chemotype for carbonic anhydrase inhibition, as well as less common non-covalent interaction types and unexpected covalent linkages. Lastly, different runs of the PanDDA tool reveal a practical hint for its application. MDPI 2020-03-29 /pmc/articles/PMC7226012/ /pubmed/32235320 http://dx.doi.org/10.3390/biom10040518 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Glöckner, Steffen
Heine, Andreas
Klebe, Gerhard
A Proof-of-Concept Fragment Screening of a Hit-Validated 96-Compounds Library against Human Carbonic Anhydrase II
title A Proof-of-Concept Fragment Screening of a Hit-Validated 96-Compounds Library against Human Carbonic Anhydrase II
title_full A Proof-of-Concept Fragment Screening of a Hit-Validated 96-Compounds Library against Human Carbonic Anhydrase II
title_fullStr A Proof-of-Concept Fragment Screening of a Hit-Validated 96-Compounds Library against Human Carbonic Anhydrase II
title_full_unstemmed A Proof-of-Concept Fragment Screening of a Hit-Validated 96-Compounds Library against Human Carbonic Anhydrase II
title_short A Proof-of-Concept Fragment Screening of a Hit-Validated 96-Compounds Library against Human Carbonic Anhydrase II
title_sort proof-of-concept fragment screening of a hit-validated 96-compounds library against human carbonic anhydrase ii
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226012/
https://www.ncbi.nlm.nih.gov/pubmed/32235320
http://dx.doi.org/10.3390/biom10040518
work_keys_str_mv AT glocknersteffen aproofofconceptfragmentscreeningofahitvalidated96compoundslibraryagainsthumancarbonicanhydraseii
AT heineandreas aproofofconceptfragmentscreeningofahitvalidated96compoundslibraryagainsthumancarbonicanhydraseii
AT klebegerhard aproofofconceptfragmentscreeningofahitvalidated96compoundslibraryagainsthumancarbonicanhydraseii
AT glocknersteffen proofofconceptfragmentscreeningofahitvalidated96compoundslibraryagainsthumancarbonicanhydraseii
AT heineandreas proofofconceptfragmentscreeningofahitvalidated96compoundslibraryagainsthumancarbonicanhydraseii
AT klebegerhard proofofconceptfragmentscreeningofahitvalidated96compoundslibraryagainsthumancarbonicanhydraseii

Ejemplares similares