Enantioresolution and Binding Affinity Studies on Human Serum Albumin: Recent Applications and Trends

Abstract

The interaction between proteins and drugs or other bioactive compounds has been widely explored over the past years. Several methods for analysis of this phenomenon have been developed and improved. Nowadays, increasing attention is paid to innovative methods, such as high performance affinity liquid chromatography (HPALC) and affinity capillary electrophoresis (ACE), taking into account various advantages. Moreover, the development of separation methods for the analysis and resolution of chiral drugs has been an area of ongoing interest in analytical and medicinal chemistry research. In addition to bioaffinity binding studies, both HPALC and ACE al-low one to perform other type of analyses, namely, displacement studies and enantioseparation of racemic or enantiomeric mixtures. Actually, proteins used as chiral selectors in chromatographic and electrophoretic methods have unique enantioselective properties demonstrating suitability for the enantioseparation of a large variety of chiral drugs or other bioactive compounds. This review is mainly focused in chromatographic and electrophoretic methods using human serum albumin (HSA), the most abundant plasma protein, as chiral selector for binding affinity analysis and enantioresolution of drugs. For both analytical purposes, updated examples are presented to highlight recent applications and current trends.

Development of a new heparan sulfate proteoglycan (HSPG) chromolith LC column to study the pH dependence binding of peptide vaccines to HSPG and role of human serum albumin on its binding

“…Indeed, after subcutaneous medication administration, UCPvax bind to HSA with a micromolar association constant ( K D – 10 μM). 5,6 UCP2 and UCP4 were thus transported to the acidic lymph node microenvironment and thus, according to our results, they decreased their binding to HSA. UCP2 and UCP4 can thus exposed favorably their polar and cationic groups to the negative net charge of heparan sulfate on immune cell surface such as DCs and CD 4+ T H 1 cells and thus may lead to T cell priming and expansion.…”

“…It was demonstrated these peptides UCP2 and UCP4 have 1 : 1 interaction at the well-known site I of HSA with similar affinities in the micromolar range ( K D ∼10 μM). 5,6 This HSA binding protected UCP2 and UCP4 from peptidase attack in LNs, through steric interference from peptidase recognition. 7 After reaching the LNs, peptide vaccine was presented on the surface of the immune cells.…”

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

“…A number of studies have been conducted by CE in which enantioselective selectors have been used as buffer additives or immobilized binding agents to separate chiral drugs [ 176 ]. This work has used buffer additives that have included proteins, polysaccharides, organic polymers, and chiral micelles, among others [ 176 , 177 , 178 ].…”

“…A number of studies have been conducted by CE in which enantioselective selectors have been used as buffer additives or immobilized binding agents to separate chiral drugs [ 176 ]. This work has used buffer additives that have included proteins, polysaccharides, organic polymers, and chiral micelles, among others [ 176 , 177 , 178 ]. Chiral separations based on CE can provide short analysis times, high efficiency, and low consumption of analytes, reagents, and solvents compared to liquid chromatography [ 176 , 178 ].…”

Chiral 8-aminoBODIPY-based fluorescent probes with site selectivity for the quantitative detection of HSA in biological samples

“…Binding site information is also relevant in applications such as chromatographic and electrophoretic enantioseparation of chiral molecules, where HSA is used as a chiral selector. 66 BODIPY-based fluorescent probes have been extensively used in sensing, imaging, theranostics, optoelectronics, etc . due to their impressive photophysical features and emission tunability.…”