Combination of Capillary Zone Electrophoresis-Mass Spectrometry, Ion Mobility-Mass Spectrometry, and Theoretical Calculations for Cysteine Connectivity Identification in Peptides Bearing Two Intramolecular Disulfide Bonds
Capillary Electrophoresis; Ion Mobility Spectrometry; Mass Spectrometry; Cysteine connectivity; Disulfide Bonds; Peptides
Abstract :
[en] Disulfide bonds between cysteine residues are commonly involved in the stability of numerous peptides and proteins and are crucial for providing biological activities. In such peptides, the appropriate cysteine connectivity ensures the proper conformation allowing an efficient binding to their molecular targets. Disulfide bond connectivity characterization is still challenging and is a critical issue in the analysis of structured peptides/proteins targeting pharmaceutical or pharmacological utilizations. This study describes the development of new and fast gas-phase and in-solution electrophoretic methods coupled to mass spectrometry to characterize the cysteine connectivity of disulfide bonds. For this purpose, disulfide isomers of three peptides bearing two intramolecular disulfide bonds but different cysteine connectivity have been investigated. Capillary zone electrophoresis and ion mobility both coupled to mass spectrometry were used to perform the separation in both aqueous and gas phases, respectively. The separation efficiency of each technique has been critically evaluated and compared. Finally, theoretical calculations were performed to support and explain the experimental data based on the predicted physicochemical properties of the different peptides.
Disciplines :
Chemistry
Author, co-author :
Delvaux, Cédric ✱; Université de Liège - ULiège > Département de chimie (sciences) > Chimie analytique inorganique
Massonnet, Philippe ✱; Université de Liège - ULiège > Département de chimie (sciences) > Chimie biologique
Kune, Christopher ; Université de Liège - ULiège > Département de chimie (sciences) > Laboratoire de spectrométrie de masse (L.S.M.)
Haler, Jean ; Université de Liège - ULiège > Département de chimie (sciences) > Chimie analytique inorganique
Upert, Gregory; Commissariat à l'Energie Atomique (Saclay) - CEA
Mourier, Gilles; Commissariat à l'Energie Atomique (Saclay) - CEA
Gilles, Nicolas; Commissariat à l'Energie Atomique (Saclay) - CEA
Quinton, Loïc ; Université de Liège - ULiège > Département de chimie (sciences) > Chimie biologique
De Pauw, Edwin ; Université de Liège - ULiège > Département de chimie (sciences) > Chimie analytique inorganique
Far, Johann ; Université de Liège - ULiège > Département de chimie (sciences) > Chimie analytique inorganique
✱ These authors have contributed equally to this work.
Language :
English
Title :
Combination of Capillary Zone Electrophoresis-Mass Spectrometry, Ion Mobility-Mass Spectrometry, and Theoretical Calculations for Cysteine Connectivity Identification in Peptides Bearing Two Intramolecular Disulfide Bonds
Publication date :
29 December 2019
Journal title :
Analytical Chemistry
ISSN :
0003-2700
eISSN :
1520-6882
Publisher :
American Chemical Society, United States - District of Columbia
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