Capillary electrophoresis as a fragment screening tool to cross-validate hits from chromogenic assay: Application to FXIIa.

Capillary electrophoresis Chromogenic assay Factor XIIa False positive Fragment-based lead discovery Serine proteinase inhibitors

Journal

Talanta
ISSN: 1873-3573
Titre abrégé: Talanta
Pays: Netherlands
ID NLM: 2984816R

Informations de publication

Date de publication:
01 May 2021
Historique:
received: 11 10 2020
revised: 20 12 2020
accepted: 25 01 2021
entrez: 7 3 2021
pubmed: 8 3 2021
medline: 8 3 2021
Statut: ppublish

Résumé

In this study, a partial-filling affinity capillary electrophoresis (pf-ACE) method was developed for the cross-validation of fragment hits revealed by chromogenic factor XIIa (FXIIa) assay. Chromogenic assay produces false positives, mainly due to spectrophotometric interferences and sample purity issues. pf-ACE was selected as counter-screening technology because of its separative character and the fact that the target does not have to be attached or tagged. The effects of protein plug length, applied voltage and composition of the running buffer were examined and optimized. Detection limit in terms of dissociation constant was estimated at 400 μM. The affinity evaluation was performed close to physiological conditions (pH 7.4, ionic strength 0.13 mol L

Identifiants

pubmed: 33676706
pii: S0039-9140(21)00084-9
doi: 10.1016/j.talanta.2021.122163
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

122163

Informations de copyright

Copyright © 2021 Elsevier B.V. All rights reserved.

Auteurs

C Davoine (C)

Namur Medicine & Drug Innovation Center (NAMEDIC - NARILIS), University of Namur, Rue de Bruxelles 61, 5000, Namur, Belgium; Laboratory for the Analysis of Medicines (LAM), Department of Pharmacy, CIRM, University of Liege, Place du 20 Août 7, 4000, Liège, Belgium.

M Fillet (M)

Laboratory for the Analysis of Medicines (LAM), Department of Pharmacy, CIRM, University of Liege, Place du 20 Août 7, 4000, Liège, Belgium.

L Pochet (L)

Namur Medicine & Drug Innovation Center (NAMEDIC - NARILIS), University of Namur, Rue de Bruxelles 61, 5000, Namur, Belgium. Electronic address: lionel.pochet@unamur.be.

Classifications MeSH