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Updated: Oct 16, 2025

A Rapid and Quantitative Fluorimetric Method for Protein-Targeting Small Molecule Drug Screening
Published on: October 16, 2015
Lysine reactivity profiling reveals molecular insights into human serum albumin-small-molecule drug interactions
Shirui Yang1,2, Wenxiang Zhang1,3, Zheyi Liu1
1CAS Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, Liaoning, China.
Abstract:
Human serum albumin (HSA) is one of the most important serum carrier proteins that deliver small-molecule drugs to their specific targets. Clarifying the molecular mechanism of the interaction between natural HSA and drugs in an aqueous solution has been a hot topic in pharmaceutical chemistry, clinical medicine, and biochemistry in recent years, but it is still challenging. In this paper, the details of molecular interactions of HSA with a variety of therapeutic drugs including ibuprofen, indomethacin, phenylbutazone, and warfarin are systematically investigated using a mass spectrometry (MS)-based lysine reactivity profiling (LRP) strategy. The results reaffirm that the major ligand binding sites (including Sites I and II) of HSA are located in subdomains IIA and IIIA, while several potential drug-binding areas at subdomain IIIB and α helix IIB-IIIA are newly characterized. The MS-LRP strategy may have important application prospects in pharmacodynamics, pharmacokinetics, and safety evaluation of small-molecule drugs.
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