scholarly journals Analysis of Binding Interactions of Ramipril and Quercetin on Human Serum Albumin: A Novel Method in Affinity Evaluation

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 547
Author(s):  
Zuzana Vaneková ◽  
Lukáš Hubčík ◽  
José Luis Toca-Herrera ◽  
Paul Georg Furtműller ◽  
Pavel Mučaji ◽  
...  
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Accurate Method ◽  
Cd Spectroscopy ◽  
Future Research ◽  
Binding Interactions ◽  
Allosteric Interactions ◽  
Flavonoid Quercetin ◽  
High Concentrations

The aim of this study was to analyze the binding interactions between a common antihypertensive drug (ramipril, R) and the widely distributed plant flavonoid quercetin (Q), in the presence of human serum albumin (HSA). From the observed fluorescence spectra of the (HSA + R) system we can assume that ramipril is also one of the Site 3 ligands—similar to fusidic acid—the binding of which has been proven by RTG crystallography. Our claim is supported by near-UV CD spectroscopy, microscale themophoresis and molecular modeling. The presence of R slightly inhibited the subsequent binding of Q to HSA and, on the contrary, the pre-incubation of HSA with Q caused a stronger binding of R, most likely due to allosteric interactions. At high concentrations, R is also able to displace Q from its binding site. The dissociation constant KD for the binding of R is more than hundredfold larger than for Q, which means that R is a very weak binder to HSA. The knowledge of qualitative and quantitative parameters of R, as well as the methods used in this study, are important for future research into HSA binding. This study shows the importance of implementing other methods for KD determination. Microscale thermophoresis has proved to be a novel, practical and accurate method for KD determination on HSA, especially in cases when fluorescence spectroscopy is unable to produce usable results.

scholarly journals The Influence of Oxidative Stress on Serum Albumin Structure as a Carrier of Selected Diazaphenothiazine with Potential Anticancer Activity

2021 ◽  
Vol 14 (3) ◽  
pp. 285
Author(s):  
Małgorzata Maciążek-Jurczyk ◽  
Beata Morak-Młodawska ◽  
Małgorzata Jeleń ◽  
Wiktoria Kopeć ◽  
Agnieszka Szkudlarek ◽  
...  
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Anticancer Activity ◽  
Drug Distribution ◽  
Cd Spectroscopy ◽  
Drug Binding ◽  
Protein Activity ◽  
Chloramine T ◽  
The Stability

Albumin is one of the most important proteins in human blood. Among its multiple functions, drug binding is crucial in terms of drug distribution in human body. This protein undergoes many modifications that are certain to influence protein activity and affect its structure. One such reaction is albumin oxidation. Chloramine T is a strong oxidant. Solutions of human serum albumin, both non-modified and modified by chloramine T, were examined with the use of fluorescence, absorption and circular dichroism (CD) spectroscopy. 10H-3,6-diazaphenothiazine (DAPT) has anticancer activity and it has been studied for the first time in terms of binding with human serum albumin—its potential as a transporting protein. Using fluorescence spectroscopy, in the presence of dansylated amino acids, dansyl-l-glutamine (dGlu), dansyl-l-proline (dPro), DAPT binding with two main albumin sites—in subdomain IIA and IIIA—has been evaluated. Based on the conducted data, in order to measure the stability of DAPT complexes with human (HSA) and oxidized (oHSA) serum albumin, association constant (Ka) for ligand-HSA and ligand-oHSA complexes were calculated. It has been presumed that oxidation is not an important issue in terms of 10H-3,6-diazaphenothiazine binding to albumin. It means that the distribution of this substance is similar regardless of changes in albumin structure caused by oxidation, natural occurring in the organism.

scholarly journals Absence of the CXCR4 Antagonist EPI-X4 from Pharmaceutical Human Serum Albumin Preparations

2021 ◽  
Author(s):  
Andrea Gilg ◽  
Mirja Harms ◽  
Lia-Raluca Olari ◽  
Ann-Kathrin Urbanowitz ◽  
Halvard Bonig ◽  
...  
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Cxcr4 Antagonist ◽  
Aspartic Proteases ◽  
Cxc Chemokine Receptor 4 ◽  
High Concentrations ◽  
Chemokine Receptor 4

Background: Endogenous Peptide Inhibitor of CXCR4 (EPI-X4) is a natural antagonist of the CXC chemokine receptor 4 (CXCR4). EPI-X4 is a 16-mer peptide that is released from human serum albumin (HSA) by acidic aspartic proteases such as Cathepsin D and E. Since human serum albumin (HSA) is an important medicinal substance we asked whether different pharmaceutical HSA products contain EPI-X4 which could have been generated during manufacturing and whether HSA can serve as a substrate for cathepsins despite of the presence of stabilizers like caprylate. Methods: Eight pharmaceutical HSA preparations representing all currently used fractionation technologies were analyzed. The previously described specific EPI-X4 ELISA was used for quantification; in vitro EPI-X4 generation by acidification in the presence or absence of cathepsins was followed by quantification with ELISA. Results: None of the pharmaceutical HSA preparations tested contained EPI-X4. Acidification of HSA did not generate EPI-X4. Addition of cathepsins D and E to acidified HSA yielded high concentrations of EPI-X4 in all HSA preparations, indistinguishable between individual products. Conclusion: Medicinal HSA preparations per se do not contain EPI-X4, but will replenish its precursor which can be cleaved to EPI-X4 in vivo, environmental conditions permitting.

scholarly journals Comparative Studies on the Human Serum Albumin Binding of the Investigational EGFR Inhibitor KP2187, Its Hypoxia-Activated Cobalt Complex, and a Series of Clinically Approved Inhibitors

Proceedings ◽  
2019 ◽  
Vol 22 (1) ◽  
pp. 27
Author(s):  
Eva Anna Enyedy ◽  
Orsolya Dömötör ◽  
Attila Borics ◽  
Bernhard K. Keppler ◽  
Christian R. Kowol
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Comparative Studies ◽  
Cobalt Complex ◽  
Albumin Binding ◽  
Egfr Inhibitor ◽  
Binding Interactions ◽  
Human Serum Albumin Binding

Binding interactions between human serum albumin and four clinically approved epidermal [...]

scholarly journals Investigation of the mechanism of binding of thiacloprid to human serum albumin using spectroscopic techniques and molecular modeling methods

2011 ◽  
Vol 25 (2) ◽  
pp. 113-122 ◽  
Author(s):  
Chuanxian Wang ◽  
Qinghua Chu ◽  
Changyun Chen ◽  
Zhao Bo
Keyword(s):  
Molecular Modeling ◽  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Electrostatic Interactions ◽  
Entropy Change ◽  
Binding Pocket ◽  
Cd Spectroscopy ◽  
Spectroscopic Techniques ◽  
Modeling Methods

Fluorescence spectroscopy, UV absorption, circular dichroism (CD) spectroscopy and molecular modeling methods were used to characterize the binding properties of thiacloprid (TL) with human serum albumin (HSA) at molecular level under physiological conditions. The fluorescence intensity of HSA decreased regularly with the gradually increasing concentration of thiacloprid. The binding constant K at three different temperatures (290, 300 and 310 K) were 3.07, 2.74 and 1.35 × 104M−1, respectively, for TL–HSA interaction have been calculated from the relevant fluorescence data. CD spectroscopic measurements have shown that the secondary structures of the protein have been changed by the interaction of thiacloprid with HSA. Furthermore, the study of molecular modeling indicated that thiacloprid could be located on the surface of the binding pocket of subdomains IIA in HSA. The hydrophobic interaction was the major acting force and there are H-bonds and electrostatic interactions between TL and HSA, which is in good agreement with the results from the experimental thermodynamic parameters (the enthalpy change ΔH0and the entropy change ΔS0were calculated to be -20.378 kJ/mol and 16.328 J/mol K according to the Van9t Hoff equation).

Molecular mechanism of tobramycin with human serum albumin for probing binding interactions: multi-spectroscopic and computational approaches

2017 ◽  
Vol 41 (16) ◽  
pp. 8203-8213 ◽  
Author(s):  
Muslim Raza ◽  
Yun Wei ◽  
Yang Jiang ◽  
Aftab Ahmad ◽  
Saleem Raza ◽  
...  
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Binding Site ◽  
Molecular Mechanism ◽  
In Silico ◽  
The Novel ◽  
Binding Interactions ◽  
Computational Approaches

Highlighting novelty: comprehensive in vitro and in silico insights for understanding the novel binding site of TOB with HSA.

The influence of the flavonoid quercetin on the interaction of propranolol with human serum albumin: Experimental and theoretical approaches

2014 ◽  
Vol 154 ◽  
pp. 229-240 ◽  
Author(s):  
Fatemeh S. Mohseni-Shahri ◽  
Mohammad R. Housaindokht ◽  
Mohammad R. Bozorgmehr ◽  
Ali A. Moosavi-Movahedi
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Theoretical Approaches ◽  
Flavonoid Quercetin
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