Journal
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
Volume 413, Issue 30, Pages 7431-7440Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s00216-021-03700-1
Keywords
Human serum albumin; HSA-drug interaction; Lysine reactivity profiling; Mass spectrometry; Proteomics
Funding
- National Natural Science Foundation of China [91853101, 81922070, 81973286]
- Natural Science Foundation of Liaoning Province [2019-YQ-07]
- Dalian Science and Technology Innovation Foundation [2019J11CY019]
- Shanghai Talent Development Fund [2019093]
- DICP [DICP I202007]
- National Key R&D Program of China [2019YFE0119300, 2018YFC1706600]
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This paper systematically investigates the molecular interactions between HSA and various therapeutic drugs using a mass spectrometry-based strategy, revealing the major ligand binding sites of HSA and newly characterized drug-binding areas. The MS-LRP strategy may have important application prospects in pharmacodynamics, pharmacokinetics, and safety evaluation of small-molecule drugs.
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 alpha 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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