Interactive Association of Drugs Binding to Human Serum Albumin

Feng Yang,Hong Liang,Yao Zhang

doi:10.3390/ijms15033580

Feng Yang, Hong Liang + Show 1 more

Open Access

https://doi.org/10.3390/ijms15033580

Copy DOI

Abstract

Human serum albumin (HSA) is an abundant plasma protein, which attracts great interest in the pharmaceutical industry since it can bind a remarkable variety of drugs impacting their delivery and efficacy and ultimately altering the drug’s pharmacokinetic and pharmacodynamic properties. Additionally, HSA is widely used in clinical settings as a drug delivery system due to its potential for improving targeting while decreasing the side effects of drugs. It is thus of great importance from the viewpoint of pharmaceutical sciences to clarify the structure, function, and properties of HSA–drug complexes. This review will succinctly outline the properties of binding site of drugs in IIA subdomain within the structure of HSA. We will also give an overview on the binding characterization of interactive association of drugs to human serum albumin that may potentially lead to significant clinical applications.

Highlights

Human serum albumin (HSA), being the most abundant protein of blood plasma, has many important physiological functions
When both fatty acids are bound to the IIA subdomain, the binding of amantadine hydrochloride (AH) is stabilized by presence of interactions of the carboxyl group of FA8 that forms hydrogen bonds with the amino group of AH (Figure 5A)
Cancer treatment is still a big challenge for humans because anticancer drugs are associated with severe side effects and an inconvenient evolution of drug resistance during treatment [101,102,103]

Summary

Introduction

Human serum albumin (HSA), being the most abundant protein of blood plasma, has many important physiological functions. Recent reported structures of HSA–ligands complexes clearly demonstrate the location of different drug binding sites on HSA, but they revealed how several drugs interact with HSA [53,73,74,75,76]. Such knowledge on the binding properties of drugs to HSA is an important issue when analyzing the mechanisms affecting the pharmacological effects of these compounds. We focused on the nature of the HSA binding sites and the mechanisms of interactive association of drugs to HSA based on the available structural evidence found on HSA–drug complexes.

Binding Site of Drugs in IIA Subdomain of HSA

Interactive Association of Drug–Drug with HSA

Interactive Association of Drug–Drug–Drug with HSA

Conclusions