ABSTRACT
Human serum albumin [HSA] is the most abundant protein constituent of blood plasma. This protein consists of a single polypeptide chain of 585 amino acid residues, which has many important physiological functions. HSA can bind and carry many drugs, including anticoagulants, tranquilizers, and general Anesthetics. Some technique such as: fluorescence spectroscopy, three-dimensional fluorescence, UV-visible, FT-IR, circular dichroism [CD], X-ray scattering [SAXS] technique and molecular modeling was utilized to investigate the effects of acceptor on conformation of the donor [HSA]. The binding site number n and apparent binding constant K[A] drugs corresponding thermodynamic parameters, the free energy change [DELTA G], enthalpy change [DELTA H], and entropy change [DELTA S] were calculated. The hydrophobic effect, van der Waals forces, hydrogen bond and electrostatic interactions play a major role in stabilizing the complex. More investigation also revealed that these drugs bind to the amino acids on the hydrophobic pocket of HSA and induce changes to the secondary structure of the HSA. In this study for better understanding of HSA-drug interactions, we categorized drugs into ten groups from years 2006 to 2012 and are suggested that two important parameters such as Delta G[0][H20] and [D] [½] can be calculated for each groups and refer to ten categories to finally indicate that fine structural change in human serum albumin
ABSTRACT
Human serum albumin has been used as a model protein for protein folding and ligand binding studies over many decades. Due to its long life period and high concentration in plasma, HSA is highly sensitive to glycation. It is reported that 175 mg/dL glucose concentration is a threshold of kidney activity for the beginning of excretion of glucose. PH denaturation of HSA in absence and presence of different concentrations of glucose is studied and based on the Pace two-state model, the findings are analyzed. In addition, florescence emission data of albumin range in the period of 300-500 nm was depicted. The amounts of free energy change and [D] [1/2] parameters of unfolding in correspond to florescence date indicate that glucose induces fine structural change in human serum albumin. Results showed that 175 mg/dL glucose concentration is a critical point for albumin structural and functional alteration
ABSTRACT
Human serum albumin [HSA] is an important protein that carries variety of substances like some hormones and drugs in blood. Pharmacological studies of the interaction of many drugs and HSA are reported during several decades, specially recently years. Interaction of cortisol and fluoxetine hydrochloride [FLX] [as a common anti-stress drug] with HSA [as their carrier in blood] has been studied separately by using different spectroscopic techniques. Here, considering the increment of anti-stress drugs consumption, conformational change of HSA in presence of cortisol and FLX in 50 mM tris buffer, at pH = 7.5 and 37°C, is investigated via pH meter, UV absorption and fluorescence spectroscopy and circular dichroism methods. pH meter findings indicate that the acid denaturation of HSA in the presence of drug and cortisol occurs in the similar manner and this pattern is different relative to the denaturation of HSA in the absence of two reagents. The results of the other techniques consistent with the pH meter findings show that FLX effects on the physiochemical properties of HSA are as that of Cortisol. In-vivo study in Rats confirms in-vitro findings which means blood cortisol level increased in the presence of FLX. Experimental results indicate that FLX and cortisol alter the structural aspects of HSA in similar manner, so, this findings lead to the following reasonable "FLX is a competitive ligand for the binding of cortisol to HSA. Binding of FLX to HSA interferes to the interaction of cortisol-HSA"