Rational design of specific ligands for human serum albumin separation and applications

Abstract

Human serum albumin is widely used in clinical practice, and the development of new ligands with high affinity is beneficial to improve its separation efficiency. The Site II of human serum albumin is an active binding site of various molecules such as l‐tryptophan, which was studied with molecular simulation to obtain insights for the design of new ligands. The results showed that the carboxyl and indolyl groups of l‐tryptophan were critical for the binding on Site II. Seven ligands containing carboxyl groups and indolyl groups were designed, and molecular simulation showed that indole‐3‐pentanoic acid was the best ligand. A new ligand combined indole‐3‐acetic acid and cysteine was designed for easier resin preparation, and molecular simulation also indicated that the new ligand bound strongly to Site II. Resins with the new ligand designed was prepared and static adsorption experiments indicated that the new resin had high adsorption capacity of human serum albumin and strong salt tolerance. Finally, recombinant human serum albumin was separated from yeast broth with high purity of 90.4% and recovery of 94.2%, which indicated that the new resin had good adsorption selectivity and strong potential for applications.

Investigation of steric hindrance effect on the interactions between four alkaloids and HSA by isothermal titration calorimetry and molecular docking

“…As a vital drug carrier, human serum albumin (HSA) is a multifunctional protein that is specifically synthesised by the liver and continuously secreted into the bloodstream. [23][24][25] It is particularly abundant in plasma, accounting for about 60% of the total plasma protein content, and its concentration ranges from 3.5 to 5.0 g/L, 26 playing a role in storage, transport and delivery. 27,28 The use of HSA as a drug carrier is encouraged by its numerous locations for selective binding to ligands or small molecules.…”