دورية أكاديمية
Comprehensive views toward the biomolecular recognition of an anticancer drug, leflunomide with human serum albumin.
| العنوان: | Comprehensive views toward the biomolecular recognition of an anticancer drug, leflunomide with human serum albumin. |
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| المؤلفون: | Kabir MZ; Faculty of Pharmacy, Department of Analytical Chemistry, Ankara University, Ankara, Turkey., Tayyab H; Faculty of Science, Bioinformatics Programme, Institute of Biological Sciences, University of Malaya, Kuala Lumpur, Malaysia., Erkmen C; Faculty of Pharmacy, Department of Analytical Chemistry, Ankara University, Ankara, Turkey., Mohamad SB; Faculty of Science, Bioinformatics Programme, Institute of Biological Sciences, University of Malaya, Kuala Lumpur, Malaysia.; Centre of Research for Computational Sciences and Informatics for Biology, Bioindustry, Environment, Agriculture and Healthcare, University of Malaya, Kuala Lumpur, Malaysia., Uslu B; Faculty of Pharmacy, Department of Analytical Chemistry, Ankara University, Ankara, Turkey. |
| المصدر: | Journal of biomolecular structure & dynamics [J Biomol Struct Dyn] 2024 Sep; Vol. 42 (14), pp. 7257-7271. Date of Electronic Publication: 2023 Aug 02. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Taylor & Francis Country of Publication: England NLM ID: 8404176 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1538-0254 (Electronic) Linking ISSN: 07391102 NLM ISO Abbreviation: J Biomol Struct Dyn Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: June 2012- : Oxon, UK : Taylor & Francis Original Publication: Guilderland, NY : Adenine Press, [c1983- |
| مواضيع طبية MeSH: | Leflunomide*/chemistry , Leflunomide*/metabolism , Molecular Docking Simulation* , Molecular Dynamics Simulation* , Protein Binding* , Serum Albumin, Human*/chemistry , Serum Albumin, Human*/metabolism , Antineoplastic Agents*/chemistry , Antineoplastic Agents*/metabolism , Thermodynamics*, Humans ; Hydrogen Bonding ; Binding Sites ; Hydrophobic and Hydrophilic Interactions ; Ligands ; Spectrometry, Fluorescence ; Isoxazoles/chemistry ; Isoxazoles/metabolism |
| مستخلص: | Biomolecular association of an anticancer drug, leflunomide (LEF) with human serum albumin (HSA), the leading ligands carrier in human circulation was characterized using biophysical ( i.e., fluorescence, absorption and voltammetric) methods and computational ( i.e., molecular docking and molecular dynamics simulation) techniques. Evaluations of fluorescence, absorption and voltammetric findings endorsed the complex formation between LEF and HSA. An inverse relationship of Stern-Volmer constant-temperature and hyperchromic shift of the protein's absorption signal with addition of LEF confirmed the LEF quenched the HSA fluorescence through static process. Moderate nature of binding strength (binding constant = 2.76-4.77 × 10 4 M -1 ) was detected towards the LEF-HSA complexation, while the association process was naturally driven via hydrophobic interactions, van der Waals interactions and hydrogen bonds, as evident from changes in entropy (Δ S = + 19.91 J mol -1 K -1 ) and enthalpy (Δ H = - 20.09 kJ mol -1 ), and molecular docking assessments. Spectral analyses of synchronous and three-dimensional fluorescence validated microenvironmental fluctuations near Trp and Tyr residues upon LEF binding to the protein. LEF association with HSA significantly defended temperature-induced destabilization of the protein. Although LEF was found to attach to HSA at Sudlow's sites I and II, but exhibited greater preference toward its site I, as detected by the investigations of competitive site-marker displacement. Molecular dynamics simulation assessment revealed that the complex attained equilibrium throughout simulations, showing the LEF-HSA complex constancy.Communicated by Ramaswamy H. Sarma. |
| فهرسة مساهمة: | Keywords: biophysical methods; computational techniques; human serum albumin; leflunomide; ligand–protein interaction |
| المشرفين على المادة: | G162GK9U4W (Leflunomide) ZIF514RVZR (Serum Albumin, Human) 0 (Antineoplastic Agents) 0 (Ligands) 0 (Isoxazoles) |
| تواريخ الأحداث: | Date Created: 20230802 Date Completed: 20240816 Latest Revision: 20240816 |
| رمز التحديث: | 20240817 |
| DOI: | 10.1080/07391102.2023.2239931 |
| PMID: | 37529911 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1538-0254 |
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| DOI: | 10.1080/07391102.2023.2239931 |