Analysis of drug interactions with serum proteins and related binding agents by affinity capillary electrophoresis: A review

Abstract

Biomolecules such as serum proteins can interact with drugs in the body and influence their pharmaceutical effects. Specific and precise methods that analyze these interactions are critical for drug development or monitoring and for diagnostic purposes. Affinity capillary electrophoresis (ACE) is one technique that can be used to examine the binding between drugs and serum proteins, or other agents found in serum or blood. This article will review the basic principles of ACE, along with related affinity-based capillary electrophoresis (CE) methods, and examine recent developments that have occurred in this field as related to the characterization of drug-protein interactions. An overview will be given of the various formats that can be used in ACE and CE for such work, including the relative advantages or weaknesses of each approach. Various applications of ACE and affinity-based CE methods for the analysis of drug interactions with serum proteins and other binding agents will also be presented. Applications of ACE and related techniques that will be discussed include drug interaction studies with serum agents, chiral drug separations employing serum proteins, and the use of CE in hybrid methods to characterize drug binding with serum proteins.

Recent developments in capillary and microchip electroseparations of peptides (2021–mid‐2023)

“…In addition to the previous chemical and enzymatic reactions of peptides, CE methods are often applied for studying of non‐covalent molecular interactions of peptides with various ligands or receptors [261] and for monitoring of formation of covalent peptide adducts with other compounds, mostly antibodies or other carrier proteins [262]. Applications of different ACE methods for the investigation of the important interactions of drugs, including peptide drugs with serum proteins and related binding agents, can be found in a recent review [145].…”

“…ACE is a combined method advantageously utilizing a high selectivity of (bio)affinity recognition/interactions and a high separation efficiency of CE. As shown in a recent reviews [144][145][146][147], ACE is widely used for investigations of non-covalent interactions of (bio)molecules including peptides under mild free-solution conditions and for the determination of the binding (association, stability, complexation, formation) constant or dissociation constant of the (bio)molecular complexes. For data processing and statistical evaluation of ACE experiments, the freely available program CEval is recommended [148].…”

“…All these methods utilize the differences in the migration velocities of the interacting species. Both theoretical and experimental aspects of these methods and their applications for estimation of the binding constants have been outlined in the above reviews [144,145,147,154]. The particular recent applications of ACE to quantitative characterizations of biopeptide interactions are presented in Section 7.3.…”

“…Various ACE modes are widely applied for determination of the association or dissociation constants of biomolecular complexes with different types of both lowand high-molecular-mass ligands including peptides, for a survey, see the recent [144,145,147] or the earlier reviews [261,295].…”

Sensitivity enhancement of capillary electrophoresis‐frontal analysis‐based method for characterization of drug‐protein interactions using on‐line sample preconcentration

“…CE-frontal analysis (CE-FA), which belongs to the group of affinity CE (ACE) modes [1], is a well-established technique for the study of different interactions. Together with mobility-shift ACE, it is one of the most used ACE modes for the characterization of plasma protein-drug bindings [2,3].…”