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

Davoine, Clara; Fillet, Marianne; Pochet, Lionel

doi:10.1016/j.talanta.2021.122163

Article (Scientific journals)

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

Davoine, Clara; Fillet, Marianne; Pochet, Lionel

2021 • In Talanta, 226

Peer Reviewed verified by ORBi

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https://hdl.handle.net/2268/258844

DOI
10.1016/j.talanta.2021.122163

PubMed
33676706

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Keywords :

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

Abstract :

[en] 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−1) in a poly (ethylene oxide)-coated capillary of 75 μm internal diameter x 33 cm length with an applied voltage of 3 kV. This method uncovered chromogenic assay's false positives due to zinc contamination. Moreover, pf-ACE supported the evaluation of compounds absorbing at 405 nm.

Research center :

CIRM - Centre Interdisciplinaire de Recherche sur le Médicament - ULiège
Namur Research Institute for Life Sciences - NARILIS

Disciplines :

Chemistry
Pharmacy, pharmacology & toxicology
Biochemistry, biophysics & molecular biology

Author, co-author :

Davoine, Clara ; Université de Liège / Université de Namur - ULiège / UNamur > CIRM / NARILIS

Fillet, Marianne ; Université de Liège - ULiège > Département de pharmacie > Analyse des médicaments

Pochet, Lionel; Université de Namur - UNamur > Department of Pharmacy > Namur research Institute for Life Sciences - NARILIS

Language :

English

Title :

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

Publication date :

01 May 2021

Journal title :

Talanta

ISSN :

0039-9140

eISSN :

1873-3573

Publisher :

Elsevier, Netherlands

Volume :

226

Peer reviewed :

Peer Reviewed verified by ORBi

Name of the research project :

Development of new compounds targeting coagulation factor XIIa using innovative microfluidic assays in the context of fragment-based drug discovery

Funders :

F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]

Available on ORBi :

since 13 April 2021

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