Lysine reactivity profiling reveals molecular insights into human serum albumin–small-molecule drug interactions
- 21 October 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Analytical and Bioanalytical Chemistry
- Vol. 413 (30), 7431-7440
- https://doi.org/10.1007/s00216-021-03700-1
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. Graphical abstractKeywords
Funding Information
- Dalian Institute of Chemical Physics (DICP I202007)
- Shanghai Talent Development Fund (2019093)
- the Dalian Science and Technology Innovation Foundation (2019J11CY019)
- Natural Science Foundation of Liaoning Province (2019-YQ-07)
- National Natural Science Foundation of China (91853101)
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