Drug Human Serum Albumin Binding Affinity Biology Essay

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The study of drug-human serum albumin binding affinity is considered as an important topic in the drug discovery and development. Capillary electrophoresis based on the principles of frontal analysis (CE-FA) is one of the most important technique, due to the short analysis time, high separation efficiency, low sample requirement, easy computerization, robustness, precision of results, low cost sample throughput and versatility to study multiple equilibria. This method is used to study the interactions between drugs and human serum albumin (HSA) and determines the binding parameters such as binding constants and the number of binding sites. Binding parameters between drugs and HSA are determined by CE-FA using commercial CE instrumentation based on the principles of zone electrophoresis. Human serum albumin (HSA) is the most copious protein in plasma and it acts as a carrier for many endogenous and exogenous compounds. The binding affinity with HSA is strongly influenced by the structural differences of the drugs. The driving forces to plasmatic proteins- flavonoids are hydrogen bonding, hydrophobic forces, steric hindrance, and spatial arrangement.

Compared with the previous 6-papers in section-3, this paper stands on very strong position due to new method employed by modifying the later methods, the physiological conditions, high efficiency CE-FA instrument (due to variations in short fused silica capillary, capillary temperature, time, pressure, and running buffer temperature).

The materials capillary, detector in the main paper are gives the good separation compared with the previous papers referenced numbers- 1, 2, 3, 4, 5, and 6 in section-3. The variations in fused silica capillary length, a new diode array UV/Vis detector, capillary rinsing time and the column temperature were used in the main paper when compared with the all the papers in section-3 and these gave the good separation results.

In the first paper in section 3 summaries characterization of interactions between polyphenolic compounds and human serum proteins by capillary electrophoresis. When compared with the original paper, this paper shown variations in the running buffer +15 kV voltage was used for the separation along with 67 mM phosphate (pH 7.4) as buffer, the hydrodynamic injection time 60 s, no reproducibility of results, no exact equation for determining the binding constant and number of binding sites and the sample equilibrated time 20 min at appropriate temperature and the binding properties between human serum albumin protein and the ten polyphenolic compounds and these binding affinities can be assessed by using ultrafiltration and capillary electrophoresis. The samples equilibrated time 30 min and less injection time give the good separation. Finally, the original paper procedure conditions are best and give the good separation and binding constants (102-104M-1).(Diniz et al., 2008)

The second paper in section 3 summaries, determination of protein-drug binding constants by pressure-assisted capillary electrophoresis (PACE)/frontal analysis (FA). When compared with the original paper, this paper shown variations in the ionic strength 0.17 M, the running buffer +15 kV voltage was used for the separation along with 67 mM phosphate (pH 7.4) as buffer, 0.5 psi external air pressure, samples injected at 1.0 psi for 40 s (~80 nL) and the concentration of free drug was calculated by using the average plateau height and by using the non-linear regression. The advantages of this paper were applied external air pressure at 0.5 psi, low samples injection at 1.0 psi for 40 s (~80 nL). Applied external air pressure at 0.5 psi gives the better separation between the drugs due to variation among charge and size ratio and it reduce the migration time, reduce the loss of drug and protein, and to achieve better drug plateau. The disadvantages of this method are at extremely high external air pressure, strongly acidic drugs, and non UV absorbing drugs are not detected by the UV spectrometry and it suitable for the binding constant less than 106 M−1 . Finally, the original paper provides the good separation and binding constants (102-104M-1). (Jia, Ramstad & Zhong, 2002)

The third paper in section 3 summaries, investigating noncovalent interactions of rutin - serum albumin by capillary electrophoresis - frontal analysis. When compared with the original paper, this paper showed small variations in the concentration of rutin, Samples injection time, and sample incubated temperature. Finally, this paper is almost similar properties with the original paper. (Lu, Ba & Chen, 2008)

The fourth paper in section 3 summaries, Study of multiple binding constants of dexamethasone with human serum albumin by capillary electrophoresis-frontal analysis and multivariate regression. When compared with the original paper, this paper showed variations in the concentration of dexamethasone, Samples injection pressure and time, and in the binding constants. The number of the binding constants and binding sites were calculated by Klotz equation and multivariate regression equations based on assumptions that there is only one type of binding site and there is two type of binding site (101M-1-104M-1). But in the original paper there is no assumption to calculate binding constant and the binding properties are justified by fluorescence spectroscopy. Finally the original paper results are better than the fourth paper. (Zhao et al., 2009)

The fifth paper in section 3 summaries, evaluation of capillary electrophoresis-frontal analysis for the study of low molecular weight drug-human serum albumin interactions. When compared with the original paper, this paper showed variations in sample injection pressure and time, temperature of the capillary, running voltage, and injection volume of the samples. The assumption was made in this paper, that the protein and complex have the same mobility, while the free drug mobility must be different from the complex mobility. The displacement experiments were studied and the concentration of HSA was kept higher than the drugs. For the increasing in the separation of the drug and human serum albumin plateau peaks, dextran was added to the run buffer. The results gave slight errors in mobility variations among free and complexed human serum albumin irrespective of the charge of the investigated low molecular weight ligands. The low sensitivity of the UV-detection system was the major problem was found in this paper. Finally, the original paper given the best result. (Østergaard et al., 2002)

The sixth paper in section 3 summaries, Protein binding study of clozapine by capillary electrophoresis in the frontal analysis mode. When compared with the main paper, this paper showed variations in (Zhou & Li, 2004)

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