scholarly journals Comparative binding character of two general anaesthetics for sites on human serum albumin

2004 ◽  
Vol 380 (1) ◽  
pp. 147-152 ◽  
Author(s):  
Renyu LIU ◽  
Qingcheng MENG ◽  
Jin XI ◽  
Jinsheng YANG ◽  
Chung-Eun HA ◽  
...  
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Hydrogen Exchange ◽  
Van Der Waals Interactions ◽  
Titration Calorimetry ◽  
Hydrogen Bond Formation ◽  
Binding Characteristics ◽  
Solution Studies ◽  
Domain Iii

Propofol and halothane are clinically used general anaesthetics, which are transported primarily by HSA (human serum albumin) in the blood. Binding characteristics are therefore of interest for both the pharmacokinetics and pharmacodynamics of these drugs. We characterized anaesthetic–HSA interactions in solution using elution chromatography, ITC (isothermal titration calorimetry), hydrogen-exchange experiments and geometric analyses of high-resolution structures. Binding affinity of propofol to HSA was determined to have a Kd of 65 µM and a stoichiometry of approx. 2, whereas the binding of halothane to HSA showed a Kd of 1.6 mM and a stoichiometry of approx. 7. Anaesthetic–HSA interactions are exothermic, with propofol having a larger negative enthalpy change relative to halothane. Hydrogen-exchange studies in isolated recombinant domains of HSA showed that propofol-binding sites are primarily found in domain III, whereas halothane sites are more widely distributed. Both location and stoichiometry from these solution studies agree with data derived from X-ray crystal-structure studies, and further analyses of the architecture of sites from these structures suggested that greater hydrophobic contacts, van der Waals interactions and hydrogen-bond formation account for the stronger binding of propofol as compared with the less potent anaesthetic, halothane.

scholarly journals Truncated human serum albumin retains general anaesthetic binding activity

2005 ◽  
Vol 388 (1) ◽  
pp. 39-45 ◽  
Author(s):  
Renyu LIU ◽  
Jinsheng YANG ◽  
Chung-Eun HA ◽  
Nadhipuram V. BHAGAVAN ◽  
Roderic G. ECKENHOFF
Keyword(s):  
Secondary Structure ◽  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Binding Sites ◽  
Expression System ◽  
Titration Calorimetry ◽  
General Anaesthetic ◽  
Solution Studies ◽  
Domain 3

Multiple binding sites for anaesthetics in HSA (human serum albumin) make solution studies difficult to interpret. In the present study, we expressed the wild-type HSA domain 3 (wtHSAd3), a peptide with two known anaesthetic binding sites in a yeast expression system. We also expressed a site-directed mutant of domain 3 (Y411Wd3). The stability and secondary structure of the constructed fragments were determined by HX (hydrogen–tritium exchange) and CD spectroscopy. The binding of two general anaesthetics, 2-bromo-2-chloro-1,1,1-trifluoroethane and propofol, to wtHSAd3 and Y411Wd3 was determined using isothermal titration calorimetry, HX and intrinsic tryptophan fluorescence quenching. Although the expressed fragments are less stable than intact wtHSA as indicated by both CD and HX, they retain the secondary structure and anaesthetic-binding characteristics of an intact HSA molecule, but with fewer binding sites. Y411Wd3 had decreased affinity for propofol but not for 2-bromo-2-chloro-1,1,1-trifluoroethane, consistent with steric hindrance. Retention of structural features and anaesthetic binding properties with fewer binding sites in this truncated protein provide feasibility for using scaled-down models of otherwise intractable systems to gain an understanding of anaesthetic binding requirements and binding–stability relationships.

Investigation of the Effects of Various Cyclodextrins on the Stabilisation of Human Serum Albumin by a Spectroscopic Method

2015 ◽  
Vol 68 (12) ◽  
pp. 1894 ◽  
Author(s):  
Mohsen Oftadeh ◽  
Golamreza Rezaei Behbahani ◽  
Ali Akbar Saboury ◽  
Shahnaz Rafiei
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Electrostatic Interactions ◽  
Spectroscopic Method ◽  
Phosphate Buffer Solution ◽  
Blue Shift ◽  
Titration Calorimetry ◽  
Tryptophan Residue ◽  
Buffer Solution

The binding parameters between cyclodextrins (CDs) and human serum albumin (HSA) were investigated by isothermal titration calorimetry (ITC), fluorescence quenching, and UV-vis absorption spectroscopy at 300 K in 50 mM phosphate buffer solution. Among the various CDs investigated, β-CD has the greater ability to decrease the aggregation of HSA and the results indicated that the inhibition order is γ-CD < α-CD < β-CD. The obtained heats for HSA+CDs interactions were reported and analysed in terms of the extended solvation model, which was used to reproduce the enthalpies of HSA interactions with CDs over a broad range of complex concentrations. The binding constant and thermodynamic parameters were obtained. These suggested that the binding reaction was driven by both enthalpy and entropy, and electrostatic interactions played a major role in the stabilising of HSA. The parameters and reflected the net effect of β-CD on the HSA stability at low and high cyclodextrin concentrations, respectively. The positive values for indicated that β-CD stabilises the HSA structure at low concentrations. The UV absorption intensity of theses complexes increased and a slight red shift was observed in the absorbance wavelength with increasing the CD concentration. The fluorescence intensity of HSA decreased regularly and a slight blue shift was observed for the emission wavelength with increasing CD concentration. The results indicate that the CD complex could quench the fluorescence of HSA and changes the microenvironment of the tryptophan residue.

scholarly journals Spectroscopic and molecular docking studies reveal binding characteristics of nazartinib (EGF816) to human serum albumin

2020 ◽  
Vol 7 (1) ◽  
pp. 191595 ◽  
Author(s):  
Abdulrahman A. Almehizia ◽  
Haitham AlRabiah ◽  
Ahmed H. Bakheit ◽  
Eman S. G. Hassan ◽  
Rashed N. Herqash ◽  
...  
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Kinase Inhibitor ◽  
Electrostatic Force ◽  
Total Binding Energy ◽  
Serum Albumins ◽  
Binding Characteristics ◽  
Theoretical Approaches ◽  
Anti Cancer

The interactions of novel anti-cancer therapeutic agents with the different plasma and tissue components, specifically serum albumins, have lately gained considerable attention due to the significant influence of such interactions on the pharmacokinetics and/or -dynamics of this important class of therapeutics. Nazartinib (EGF 816; NAZ) is a new anti-cancer candidate proposed as a third-generation epidermal growth factor receptor tyrosine kinase inhibitor that is being developed and clinically tested for the management of non-small cell lung cancer. The current study aimed to characterize the interaction between NAZ and human serum albumin (HSA) using experimental and theoretical approaches. Experimental results of fluorescence quenching of HSA induced by NAZ revealed the development of a statically formed complex between NAZ and HSA. Interpretation of the observed fluorescence data using Stern–Volmer, Lineweaver–Burk and double-log formulae resulted in binding constants for HSA-NAZ complex in the range of (2.34–2.81) × 10 4 M –1 over the studied temperatures. These computed values were further used to elucidate thermodynamic attributes of the interaction, which showed that NAZ spontaneously binds to HSA with a postulated electrostatic force-driven interaction. This was further verified by theoretical examination of the NAZ docking on the HSA surface that revealed an HSA-NAZ complex where NAZ is bound to HSA Sudlow site I driven by hydrogen bonding in addition to electrostatic forces in the form of pi-H bond. The HSA binding pocket for NAZ was shown to encompass ARG 257, ARG 222, LYS 199 and GLU 292 with a total binding energy of −25.59 kJ mol –1 .

scholarly journals Insight of the Interaction between 2,4-thiazolidinedione and Human Serum Albumin: A Spectroscopic, Thermodynamic and Molecular Docking Study

2019 ◽  
Vol 20 (11) ◽  
pp. 2727 ◽  
Author(s):  
Safikur Rahman ◽  
Md Tabish Rehman ◽  
Gulam Rabbani ◽  
Parvez Khan ◽  
Mohamed F AlAjmi ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Docking Study ◽  
Dynamics Simulation ◽  
Titration Calorimetry ◽  
Peroxisome Proliferator ◽  
Molecular Docking Study ◽  
Fluorescence Studies

Thiazolidinedione derivatives (TZDs) have attracted attention because of their pharmacological effects. For example, certain TZDs have been reported to ameliorate type II diabetes by binding and activating PPARs (peroxisome proliferator-activated receptors). Nonetheless, no information is available on the interaction between the heterocyclic 2, 4-thiazolidinedione (2,4-TZD) moiety and serum albumin, which could affect the pharmacokinetics and pharmacodynamics of TZDs. In this study, we investigated the binding of 2,4-TZD to human serum albumin (HSA). Intrinsic fluorescence spectroscopy revealed a 1:1 binding stoichiometry between 2,4-TZD and HSA with a binding constant (Kb) of 1.69 ± 0.15 × 103 M−1 at 298 K. Isothermal titration calorimetry studies showed that 2,4-TZD/HSA binding was an exothermic and spontaneous reaction. Molecular docking analysis revealed that 2,4-TZD binds to HSA subdomain IB and that the complex formed is stabilized by van der Waal’s interactions and hydrogen bonds. Molecular dynamics simulation confirmed the stability of the HSA-TZD complex. Further, circular dichroism and 3D fluorescence studies showed that the global conformation of HSA was slightly altered by 2,4-TZD binding, enhancing its stability. The results obtained herein further help in understanding the pharmacokinetic properties of thiazolidinedione.

Localization of Tolbutamide Binding Sites on Human Serum Albumin Using Titration Calorimetry and Heteronuclear 2-D NMR

Biochemistry ◽  
1995 ◽  
Vol 34 (27) ◽  
pp. 8780-8787 ◽  
Author(s):  
Michael G. Jakoby ◽  
Douglas F. Covey ◽  
David P. Cistola
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Binding Sites ◽  
Titration Calorimetry

scholarly journals A Comparative Interaction between Copper Ions with Alzheimer'sβAmyloid Peptide and Human Serum Albumin

2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
G. Rezaei Behbehani ◽  
L. Barzegar ◽  
M. Mohebbian ◽  
A. A. Saboury
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Copper Ions ◽  
Copper Ion ◽  
Titration Calorimetry ◽  
Solvation Model ◽  
Solvation Parameters ◽  
Induced Aggregation

The interaction of Cu2+with the first 16 residues of the Alzheimer's amyliodβpeptide,Aβ(1–16), and human serum albumin (HSA) were studied in vitro by isothermal titration calorimetry at pH 7.2 and 310 K in aqueous solution. The solvation parameters recovered from the extended solvation model indicate that HSA is involved in the transport of copper ion. Complexes betweenAβ(1–16) and copper ions have been proposed to be an aberrant interaction in the development of Alzheimer's disease, where Cu2+is involved inAβ(1–16) aggregation. The indexes of stability indicate that HSA removed Cu2+fromAβ(1–16), rapidly, decreased Cu-induced aggregation ofAβ(1–16), and reduced the toxicity ofAβ(1–16) + Cu2+significantly.

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