Akademik Veri Yönetim Sistemi
SPECTROCHIMICA ACTA - PART A: MOLECULAR AND BIOMOLECULAR SPECTROSCOPY, cilt.322, sa.124818, ss.1-13, 2024 (SCI-Expanded)
The interaction between Nitisinone (NTBC) and bovine serum albumin (BSA) as the transport protein in a circulating system was investigated for the first time utilizing various analytical (UV–Vis spectrophotometry, fluorescence spectroscopy, dynamic light scattering, and differential scanning calorimetry) and computational (molecular docking and molecular dynamics simulations) methods. The BSA fluorescence intensity was quenched upon interaction with NTBC, and the quenching mechanism was observed as static. The interaction between NTBC and BSA was examined at 288 K, 298 K, and 308 K where the binding constants were found to be 1.44 × 105 ± 0.22 M−1, 5.18 × 104 ± 0.20 M−1, and 3.02 × 104 ± 0.22 M−1 respectively, suggesting an intermediate binding affinity between NTBC and BSA. Changes in the microenvironment surrounding tryptophan and tyrosine residues of BSA were elucidated using 3-D fluorescence spectroscopy. Thermodynamic studies revealed the calculated values of ΔH = − 54.34 ± 5 kJ/mol and ΔS = − 0.0908 ± 0.24 kJ/mol K−1, indicating the involvement of van der Waals forces and hydrogen bonds in the interaction between NTBC and BSA. Moreover, the interaction’s spontaneous nature was evidenced by negative ΔG values across all temperatures. Using dynamic light scattering, it was observed that higher NTBC concentrations led to a gradual rise in hydrodynamic diameter and notable aggregation of the NTBC-BSA complex. Moreover, changing signal values and shifted peaks of BSA, NTBC, and complex in differential scanning calorimetry curves, meant there were molecular interactions between the NTBC and BSA. In silico approaches also elucidated how NTBC binds to active sites on BSA, further supporting other findings. Moreover, molecular docking studies offer a more profound insight into the changing dynamics of hydrophobic, hydrogen, and halogen bonding involved in stabilizing the NTBC-BSA complex.