Abstract
Human serum albumin (HSA) is the most abundant human plasma protein. HSA plays a crucial role in many binding endos- and exogenous substances, which affects their pharmacological effect. The innovative aspect of the study is not only the interaction of fatted (HSA) and defatted (dHSA) human serum albumin with ibuprofen (IBU), but the analysis of the influence of temperature on the structural modifications of albumin and the interaction between the drug and proteins from the temperature characteristic of near hypothermia (308 K) to the temperature reflecting inflammation in the body (312 K and 314 K). Ibuprofen is a non-steroidal anti-inflammatory drug. IBU is used to relieve acute pain, inflammation, and fever. To determine ibuprofen’s binding site in the tertiary structure of HSA and dHSA, fluorescence spectroscopy was used. On its basis, the fluorescent emissive spectra of albumin (5 × 10−6 mol/dm3) without and with the presence of ibuprofen (1 × 10−5–1 × 10−4 mol/dm3) was recorded. The IBU-HSA complex’s fluorescence was excited by radiation of wavelengths of λex 275 nm and λex 295 nm. Spectrophotometric spectroscopy allowed for recording the absorbance spectra (zero-order and second derivative absorption spectra) of HSA and dHSA under the influence of ibuprofen (1 × 10−4 mol/dm3). To characterize the changes of albumin structure the presence of IBU, circular dichroism was used. The data obtained show that the presence of fatty acids and human serum albumin temperature influences the strength and type of interaction between serum albumin and drug. Ibuprofen binds more strongly to defatted human serum albumin than to albumin in the presence of fatty acids. Additionally, stronger complexes are formed with increasing temperatures. The competitive binding of ibuprofen and fatty acids to albumin may influence the concentration of free drug fraction and thus its therapeutic effect.
Highlights
Serum albumin is the most frequently occurring protein in blood plasma [1,2,3]
Their results indicate that the fatty acids present in human serum albumin contribute to changing the conformation of the protein structure and modify individual ligand binding to albumin and interaction between the ligands [24]
At the temperature of 310 K, the absorbance of fatted and defatted albumin after binding with ibuprofen increased significantly. This proves that the presence of fatty acids has no influence on the interaction between the protein and the drug at the temperature corresponding to physiological conditions
Summary
Serum albumin is the most frequently occurring protein in blood plasma [1,2,3]. A standard concentration of albumin in plasma is in the range of 35–45 g/L [4,5]. Human serum albumin (HSA) forms a heart-shaped molecule consist of 585 amino acid residues. Crystal structure analysis of human serum albumin revealed that HSA contains three homologous domains (I–III). All domains are divided into two subdomains A and B, composed of four and six α-helices [1,6]. Human serum albumin exhibits the ability to bind many endogenous and exogenous ligands such as drugs, fatty acids, amino acids, hormones, vitamins [5,7,8]
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