Interaction mechanism of a cysteine protease inhibitor, odanacatib, with human serum albumin: In vitro and bioinformatics studies.

Autor: Asngari NJM; Department of Oral & Craniofacial Sciences, Faculty of Dentistry, Universiti Malaya, 50603 Kuala Lumpur, Malaysia., Bakar KA; Department of Biological Sciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor, Malaysia., Feroz SR; Department of Biological Sciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor, Malaysia., Razak FA; Department of Oral & Craniofacial Sciences, Faculty of Dentistry, Universiti Malaya, 50603 Kuala Lumpur, Malaysia; Adjunct Professor, Faculty of Dentistry, Universitas Padjadjaran, Bandung, Indonesia., Halim AAA; Department of Oral & Craniofacial Sciences, Faculty of Dentistry, Universiti Malaya, 50603 Kuala Lumpur, Malaysia. Electronic address: adyaniazizah@um.edu.my.
Jazyk: angličtina
Zdroj: Biophysical chemistry [Biophys Chem] 2024 Feb; Vol. 305, pp. 107140. Date of Electronic Publication: 2023 Nov 10.
DOI: 10.1016/j.bpc.2023.107140
Abstrakt: Odanacatib (ODN) is a selective cathepsin K inhibitor that acts as an anti-resorptive agent to treat osteoporosis. ODN is also found effective in reducing the effect of severe periodontitis. The interaction between ODN and human serum albumin (HSA) was investigated using spectroscopic, microscopic, and in silico approaches to characterize their binding. The fluorescence intensity of HSA increased upon the addition of increasing concentrations of ODN accompanied by blueshift in the fluorescence spectrum, which suggested hydrophobic formation around the microenvironment of the fluorophores upon ODN binding. A moderate binding affinity was obtained for ODN-HSA binding, with binding constant (K a ) values of ∼10 4  M -1 . Circular dichroism results suggested that the overall secondary and tertiary structures of HSA were both only slightly altered upon ODN binding. The surface morphology of HSA was also affected upon ODN binding, showing aggregate formation. Drug displacement and molecular docking results revealed that ODN preferably binds to site III in subdomain IB of HSA, while molecular dynamics simulations indicated formation of a stable protein complex when site III was occupied by ODN. The ODN-HSA complex was mainly stabilized by a combination of hydrogen bonding, hydrophobic interactions, and van der Waals forces. These findings provide additional information to understand the interaction mechanism of ODN in blood circulation and may help in future improvements on the adverse effects of ODN.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Adyani Azizah Abd Halim reports financial support was provided by University of Malaya.
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Databáze: MEDLINE