Title :

Antagonists of the P2X7 receptor: Mechanism of enantioselective recognition using highly sulfated and sulfobutylether cyclodextrins by capillary electrokinetic chromatography

Author(s) :

Baudelet, Davy [Auteur]
Ghinet, Alina [Auteur]
Furman, Christophe [Auteur]
Dezitter, Xavier [Auteur]
Gautret, Philippe [Auteur]
Rigo, Benoit [Auteur]
MILLET, Régis [Auteur]
Vaccher, Claude [Auteur]
Lipka, Emmanuelle [Auteur]

Journal title :

Electrophoresis

Abbreviated title :

Electrophoresis

Volume number :

35

Pages :

2892-2899

Publication date :

2014-10-01

ISSN :

0173-0835
1522-2683

English keyword(s) :

Cyclodextrins
Thermodynamic parameters
Complexation
Binding constant
Enantiomer

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

This work concerns the successful enantiomeric separation of pyroglutamic acid derivatives, known to be P2X7 receptor antagonists, achieved by electrokinetic chromatography. After a broad screening, two negatively charged ...
Show more >This work concerns the successful enantiomeric separation of pyroglutamic acid derivatives, known to be P2X7 receptor antagonists, achieved by electrokinetic chromatography. After a broad screening, two negatively charged cyclodextrins, sulfobutylether-β-cyclodextrin (SBE-β-CD), and highly sulfated-γ-cyclodextrin (HS-γ-CD) were chosen as stereoselective agents to cooperate with the BGE for complexation. A fused silica capillary coated with polyethylene oxide, filled with a phosphate buffer (25 mM, pH 2.5) containing various concentrations of CD, was used. Assuming a 1:1 stoichiometry, calculations of the binding constants, employing the three different linearization plots, were performed from the corrected electrophoretic mobilities values of the enantiomers, at different concentrations of SBE-β-CD and HS-γ-CD in the BGE. The highest complexation was found with the SBE-β-CD. Among the three equations, results showed better linearity (R(2) > 0.99) using the y-reciprocal fit. This plotting method was then performed to determine the binding constants of each enantiomer at different temperature for compounds 1 and 2 with SBE-β-CD and HS-γ-CD in order to access to the thermodynamic parameters of the eight complexes. The linearity of the Van't Hoff plot, in the range of 288-303 K leading to negative enthalpy values, showed that the complexation phenomenon is enthalpically controlled and thermodynamically favored.Show less >

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

CHU Lille
Inserm
Université de Lille

Collections :

• Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286

Research team(s) :

Therapeutic innovation targetting inflammation

Submission date :

2019-05-17T13:14:33Z