摘要 :
Serum albumin, a protein naturally abundant in blood plasma, shows remarkable ligand binding properties of numerous endogenous and exogenous compounds. Most of serum albumin binding sites are able to interact with more than one cl...
展开
Serum albumin, a protein naturally abundant in blood plasma, shows remarkable ligand binding properties of numerous endogenous and exogenous compounds. Most of serum albumin binding sites are able to interact with more than one class of ligands. Determining the protein-ligand interactions among mammalian serum albumins is essential for understanding the complexity of this transporter. We present three crystal structures of serum albumins in complexes with naproxen (NPS): bovine (BSA-NPS), equine (ESA-NPS), and leporine (LSA-NPS) determined to 2.58 ? (C2), 2.42 ? (P61), and 2.73 ? (P212121) resolutions, respectively. A comparison of the structurally investigated complexes with the analogous complex of human serum albumin (HSA-NPS) revealed surprising differences in the number and distribution of naproxen binding sites. Bovine and leporine serum albumins possess three NPS binding sites, but ESA has only two. All three complexes of albumins studied here have two common naproxen locations, but BSA and LSA differ in the third NPS binding site. None of these binding sites coincides with the naproxen location in the HSA-NPS complex, which was obtained in the presence of other ligands besides naproxen. Even small differences in sequences of serum albumins from various species, especially in the area of the binding pockets, influence the affinity and the binding mode of naproxen to this transport protein.
收起
摘要 :
Fluorescence studies on furosemide (FUR) binding to bovine serum albumin (BSA) showed the existence of three or four binding sites in the tertiary structure of the protein. Two of them are located in subdomain IIA, while the other...
展开
Fluorescence studies on furosemide (FUR) binding to bovine serum albumin (BSA) showed the existence of three or four binding sites in the tertiary structure of the protein. Two of them are located in subdomain IIA, while the others in subdomains IB and/or IIIA. Furosemide binding in subdomain IB is postulated on the basis of run of Stern–Volmer plot indicating the existence of two populations of tryptophans involved in the interaction with FUR. In turn, the significant participation of tyrosil residues in complex formation leads to the consideration of the subdomain IIIA as furosemide low-affinity binding site. The effect of increasing concentration of fatty acid on FUR binding in all studied binding sites was also investigated and compared with the previous results obtained forhumanserum albumin (HSA). ForBSAthe lesser impact of fatty acid on affinity between drug and albumin was observed. This is probably a result of more significant role of tyrosines in the complex formation and different polarity of microenvironment of the fluorophores when compared HSA and BSA. The most distinct differences between FUR–BSA and FUR–HSA binding parameters are observedwhenthird fatty acid molecule is bound with the protein and rotation of domains I and II occurs. However these structural changes mostly affect FUR low affinity binding sites.
收起
摘要 :
Serum albumins are evolutionary conserved proteins that are found in many animal species, and purified forms are widely used in biotechnology applications, such as components within surface passivation coatings and drug delivery s...
展开
Serum albumins are evolutionary conserved proteins that are found in many animal species, and purified forms are widely used in biotechnology applications, such as components within surface passivation coatings and drug delivery systems. As such, there has long been interest in studying how serum albumins adsorb onto solid supports, although existing studies are limited to one or two species. Herein, we comprehensively investigated three serum albumins of bovine (BSA), human (HSA), and rat (RSA) origin, and discovered striking differences in their conformational stabilities and adsorption properties. Together with bioinformatics analysis, dynamic light scattering (DLS) and circular dichroism (CD) spectroscopy measurements revealed that the proteins form different types of macromolecular assemblies in solution. BSA and HSA existed as individual monomers while RSA formed multimers, and each protein exhibited sequence-dependent variations in conformational stability as well. Quartz crystal microbalance-dissipation (QCM-D) and localized surface plasmon resonance (LSPR) experiments further showed that BSA and HSA proteins adsorb to form well-packed adlayers, and the extent of protein uptake and spreading depended on their unique conformational stabilities. Conversely, RSA adsorption resulted in sparse adlayers and appreciably less spreading of the adsorbed multimers, as confirmed by attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy experiments. Together, our findings demonstrate that significant differences in conformational stability and adsorption behavior exist even between evolutionary conserved serum albumins with high sequence and structural similarity and illustrate how rational engineering of protein structures and stabilities, guided by insights from nature, might be useful to design protein-based coatings for various biointerfacial science applications.
收起
摘要 :
Serum albumin (SA) is the most abundant carrier protein in blood. SA carries a diverse range of nutrients, drugs, and metal ions. It has wide clinical and biochemical applications. Human serum albumin (HSA) can be used as a biomar...
展开
Serum albumin (SA) is the most abundant carrier protein in blood. SA carries a diverse range of nutrients, drugs, and metal ions. It has wide clinical and biochemical applications. Human serum albumin (HSA) can be used as a biomarker for kidney and liver diseases. Aptasensor is one of potential HSA detection methods. HSA-specific aptamer was selected for HSA detection. In animals, bovine serum albumin (BSA) and canine serum albumins (CSA) share high sequence similarities to HSA. Thus, it is interesting to explore the possibility of using HSA-selective aptamer for BSA and CSA aptasensor. In this study, molecular dynamics (MD) simulations were initially employed to investigate the binding of aptamer to BSA and CSA in comparison to HSA. Like HSA, both BSA and CSA can bind aptamer, but different binding affinities are observed. BSA shows the tighter binding to aptamer than CSA. Domain III is found to be the aptamer-binding domain although no specific aptamer conformation is captured. However, in all cases, the aptamer utilizes the 3 '-end to attach on an albumin surface. Both nucleobases and phosphate backbones on a DNA aptamer are important for albumin-aptamer complexation. Our results imply the possibility of using HSA-specific aptamer for BSA detection due to tighter binding observed, but may be less effective in CSA. However, the test in actual complicated condition must be further studied.
收起
摘要 :
Albumin is known as being able to cleave ester bonds in organophosphates (OP) and serve as a major means of OP detoxification due to its large amount in the blood serum. Most of in vivo toxicological studies are conducted on roden...
展开
Albumin is known as being able to cleave ester bonds in organophosphates (OP) and serve as a major means of OP detoxification due to its large amount in the blood serum. Most of in vivo toxicological studies are conducted on rodents, mice and rats. To adequately extrapolate results of ligand/albumin interaction studies to a human organism, it is necessary to carry out a comparative analysis of the rat (RSA) and human (HSA) albumin structure by in silico methods. X-ray diffraction analysis of RSA has not been done as yet, and the RSA structure is still undetermined. The aim of this study was to build a three-dimensional (3D) model of RSA by homology modeling. As templates, 14 RSA homologs were selected from the Protein Data Bank. A 3D model of the RSA molecule was built using the RSA primary sequence and 3D models of the selected templates. The 3D model geometry was improved by the energy minimization method. The quality of the model was evaluated by 9 parameters. According to this evaluation, in 97% of protein structures from the comparative dataset these parameters were worse than in the obtained model. It was concluded that this model is suitable for further research, specifically, for in silico studies of the RSA/OP interaction and comparative evolutionary analysis of RSA and HSA.
收起
摘要 :
Albumin is a biocompatible, non-immunogenic and versatile drug carrier system. It has been widely used to extend the half-life, enhance stability, provide protection from degradation and allow specific targeting of therapeutic age...
展开
Albumin is a biocompatible, non-immunogenic and versatile drug carrier system. It has been widely used to extend the half-life, enhance stability, provide protection from degradation and allow specific targeting of therapeutic agents to various disease states. Understanding the role of albumin as a drug delivery and distribution system has increased remarkably in the recent years from the development of albumin-binding prodrugs to albumin as a drug carrier system. The extraordinary surface property of albumin makes it possible to bind various endogenous and exogenous molecules. This review succinctly deals with several albumin-drug conjugates and nanoparticles along with their preparation techniques and focuses on surface-modified albumin and targeting of albumin formulation to specific organs and tissues. It also summarizes research efforts on albumin nanoparticles used for delivering drugs to tumor cells and describes their role in permeation through tumor vasculature and in receptor mediated endocytosis, which is also described in this review. The versatility of albumin and ease of preparation makes it a suitable drug carrier system, swhich is the major objective of this review.
收起
摘要 :
The objective of the study was to investigate the effects of plasma viscosity after hemodilution on the thickness of the erythrocyte cell free layer (CFL) and on the interface between the flowing column of erythrocytes and the vas...
展开
The objective of the study was to investigate the effects of plasma viscosity after hemodilution on the thickness of the erythrocyte cell free layer (CFL) and on the interface between the flowing column of erythrocytes and the vascular endothe-lium. The erythrocyte CFL thickness was measured in the rat cremaster muscle preparation. Plasma viscosity was modified in an isovolemic hemodilution, in which the systemic hematocrit (Hct_(sys)) was lowered to 30%. The plasma expanders (PE) of similar nature and different viscosities were generated by glutaraldehyde polymerization of human serum albumin (HSA) at various molar ratios glutaraldehyde to HSA: (ⅰ) unpolymerized HSA; (ⅱ) PolyHSA_(24:1), molar ratio = 24 and (ⅲ) PolyHSA_(60:1) molar ratio = 60. The HSA viscosities determined at 200 s~(-1) were 1.1, 4.2 and 6.0 dyn · cm~(-2), respectively. CFL thickness, vessel diameter and blood flow velocity were measured, while volumetric flow, shear rate and stress were calculated. Hemodilution with PolyHSA_(60:1) increased plasma viscosity and the blood showed marked shear thinning behavior. CFL thickness decreased as plasma viscosity increased after hemodilution; thus the CFL thickness with HSA and PolyHSA_(24:1) increased compared to baseline. Conversely, the CFL thickness of PolyHSA_(60:1) was not different from baseline. Blood flow increased with both PolyHSA's compared to baseline. Wall shear rate and shear stress increased for PolyHSA_(60:1) compared to HSA and PolyHSA_(24:1), respectively. In conclusion, PE viscosity determined plasma viscosity after hemodilution and affected erythrocyte column hydrodynamics, changing the velocity profile, CFL thickness, and wall shear stress. This study relates the perfusion caused by PolyHSA_(60:1) to hemodynamic changes induced by the rheological properties of blood diluted with PolyHSA_(60:1)
收起
摘要 :
In this project, our research group has performed an interesting work in which interactions of acarbose (ACB) with normal human serum albumin (HSA) and glycated HSA (GHSA) have been investigated by chemometrics assisted-electroche...
展开
In this project, our research group has performed an interesting work in which interactions of acarbose (ACB) with normal human serum albumin (HSA) and glycated HSA (GHSA) have been investigated by chemometrics assisted-electrochemical and spectroscopic techniques. To have a deep insight to the interactions of ACB with HSA and GHSA, different electrochemical and spectroscopic techniques were used to monitor ACB-HSA and ACB-GHSA interactions and analyzed by multivariate curve resolution alternating least squares (MCR-ALS), MCR-BANNDS and EQUISPEC as efficient chemometric algorithms. Then, molecular docking techniques were used to extract more information which helped us to better justify binding of ACB with HSA and GHSA. After obtaining qualitative and quantitative information and justification of the ACB-HSA and ACB-GHSA interactions, a novel electrochemical technique was developed for exploiting second-order advantage from differential pulse voltammetric data for determination of GHSA as a potential biomarker in diabetes in the presence of HSA. Calibration and validation of the developed system showed us that our system was successful in determination of GHSA in synthetic and real samples.
收起
摘要 :
Biodegradable polymers are drawing a great deal of attention in the field of nanotechnology. Albumin, abundantly present in human body, is a biocompatible and biodegradable polymer used in drug delivery systems. It is relatively a...
展开
Biodegradable polymers are drawing a great deal of attention in the field of nanotechnology. Albumin, abundantly present in human body, is a biocompatible and biodegradable polymer used in drug delivery systems. It is relatively an inexpensive polymer with several advantages like non-toxicity, high drug loading capacity, binding efficiency with many drugs which qualifies it as an ideal nanocarrier. The present review discusses potential of albumin nanocarriers for pulmonary application. It also discusses feasibility of employing albumin from different sources. Formulation aspects of albumin nanosystems, methods of preparation and dosage form designing are also covered. An array of excipient options suitable to be used in albumin nanocarrier system is presented. Toxicity aspects and applications of albumin nanoparticles with focus on pulmonary application are highlighted. Application of nanoparticulate structures based on albumin in delivery of drugs from category of anticancer agents, vaccines, hormones, anti-asthamatics and anti-inflammatory agents to lungs is covered. This review offers a framework for pharmaceutical scientists in designing of albumin nanoparticles for various pulmonary and systemic applications via inhalation delivery.
收起
摘要 :
Swertisin (6-glucosyl flavonoid) and spinosin (2 ''-beta-O-glucopyranosyl swertisin) are two main components from Ziziphi Spinosae Semen, with anti-anxiety and hypnosis effects. The paper aims to compare the differences between th...
展开
Swertisin (6-glucosyl flavonoid) and spinosin (2 ''-beta-O-glucopyranosyl swertisin) are two main components from Ziziphi Spinosae Semen, with anti-anxiety and hypnosis effects. The paper aims to compare the differences between the two compounds binding with serum albumins (BSA and HSA). Swertisin and spinosin statically quench intrinsic fluorescence of serum proteins by binding to proteins to form complexes. The fluorescence quenching rates of BSA induced by swertisin or spinosin are faster than those of HSA resulted by swertisin or spinosin, respectively. Each serum protein has only one binding site respectively accessible to the two compounds. Hydrophobic force and hydrogen bond play the important roles during the biding process of swertisin with proteins, but van der Waals force and hydrogen bond are major driving forces for spinosin binding to proteins. Synchronous fluorescence data show that spinosin binds to BSA and HSA and thus changes Tyr and Trp residue microenvironments, and has a greater effect on the latter. Compared with swertisin, spinosin has a stronger effect on the alpha-helix of proteins. But the distance between swertisin and proteins is slightly closer than spinosin. These findings will contribute to further understand the reaction of Ziziphi Spinosae Semen in the liver phase I oxidation, intestinal hydrolysis and deparaffin metabolism.
收起
原文获取