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Target-directed Dynamic Combinatorial Chemistry: A Study on Potentials and Pitfalls as Exemplified on a Bacterial Target

Frei, Priska and Pang, Lijuan and Silbermann, Marleen and Eriş, Deniz and Mühlethaler, Tobias and Schwardt, Oliver and Ernst, Beat. (2017) Target-directed Dynamic Combinatorial Chemistry: A Study on Potentials and Pitfalls as Exemplified on a Bacterial Target. Chemistry - A European Journal, 23 (48). pp. 11570-11577.

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Official URL: http://edoc.unibas.ch/55826/

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Abstract

Target-directed dynamic combinatorial chemistry (DCC) is an emerging technique for the efficient identification of inhibitors of pharmacologically relevant targets. In this contribution, we present an application for a bacterial target, the lectin FimH, a crucial virulence factor of uropathogenic E. coli being the main cause of urinary tract infections. A small dynamic library of acylhydrazones was formed from aldehydes and hydrazides and equilibrated at neutral pH in presence of aniline as nucleophilic catalyst. The major success factors turned out to be an accordingly adjusted ratio of scaffolds and fragments, an adequate sample preparation prior to HPLC analysis, and the data processing. Only then did the ranking of the dynamic library constituents correlate well with affinity data. Furthermore, as a support of DCC applications especially to larger libraries, a new protocol for improved hit identification was established.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Molekulare Pharmazie (Ernst)
UniBasel Contributors:Ernst, Beat and Frei, Priska and Pang, Lijuan and Silbermann, Marleen and Eris, Deniz and Mühlethaler, Tobias and Schwardt, Oliver
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Wiley
ISSN:0947-6539
e-ISSN:1521-3765
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:28 Nov 2017 11:17
Deposited On:20 Oct 2017 09:05

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