scholarly journals Human Serum Albumin Aggregation/Fibrillation and its Abilities to Drugs Binding

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 618 ◽  
Author(s):  
Małgorzata Maciążek-Jurczyk ◽  
Kamil Janas ◽  
Jadwiga Pożycka ◽  
Agnieszka Szkudlarek ◽  
Wojciech Rogóż ◽  
...  
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Conformational Changes ◽  
Binding Sites ◽  
Amyloid Fibrils ◽  
Cd Spectroscopy ◽  
Dansyl Amino Acids ◽  
Ph Conditions

Human serum albumin (HSA) is a protein that transports neutral and acid ligands in the organism. Depending on the environment’s pH conditions, HSA can take one of the five isomeric forms that change its conformation. HSA can form aggregates resembling those in vitro formed from amyloid at physiological pH (neutral and acidic). Not surprisingly, the main goal of the research was aggregation/fibrillation of HSA, the study of the physicochemical properties of formed amyloid fibrils using thioflavin T (ThT) and the analysis of ligand binding to aggregated/fibrillated albumin in the presence of dansyl-l-glutamine (dGlu), dansyl-l-proline (dPro), phenylbutazone (Phb) and ketoprofen (Ket). Solutions of human serum albumin, both non-modified and modified, were examined with the use of fluorescence, absorption and circular dichroism (CD) spectroscopy. The experiments conducted allowed observation of changes in the structure of incubated HSA (HSAINC) in relation to nonmodified HSA (HSAFR). The formed aggregates/fibrillation differed in structure from HSA monomers and dimers. Based on CD spectroscopy, previously absent β-structural constructs have been registered. Whereas, using fluorescence spectroscopy, the association constants differing for fresh and incubated HSA solutions in the presence of dansyl-amino acids and markers for binding sites were calculated and allowed observation of the conformational changes in HSA molecule.

Human Serum Albumin aggregation and its modulation using nanoparticles: A review

2021 ◽  
Vol 28 ◽  
Author(s):  
Santhosh Paramasivam ◽  
Kavita Kundal ◽  
Nandini Sarkar
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Conformational Changes ◽  
Extracellular Fluid ◽  
Circulatory System ◽  
Chemical Properties ◽  
Suitable Model ◽  
Amyloid Formation

: Amyloid fibrils are highly stable protein fibrillar aggregates believed to be involved in various neurodegenerative diseases, which include Alzheimer’s disease, Parkinson’s disease, and prion diseases. Inhibiting the aggregation process is a potential strategy to prevent diseases caused by amyloid formation. In this regard, nanoparticles have emerged as promising candidates owing to their unique physical/chemical properties of small size, large surface area, biocompatibility, biodegradability, non-toxicity, and ease of functionalization. Human Serum Albumin (HSA) is a soluble multidomain monomeric protein that interacts with various ligands and hormones, aiding in their transport, distribution, metabolism in the circulatory system, and also plays a vital role in extracellular fluid volume stabilization. Under certain in vitro conditions, HSA has been reported to undergo conformational changes leading to fibril formation and hence acts as a suitable model for studying amyloidogenesis. In this review, we have explored the effects of various nanoparticles on HSA aggregation and their mechanism of action. The study will throw light on the mechanistic details of nanoparticle-mediated amyloid modulation, which will help in the development of effective therapeutics against amyloidosis.

Effect of ageing of human serum albumin in vitro on surface hydrophobicity and binding sites of metronidazole

2011 ◽  
Vol 993 (1-3) ◽  
pp. 477-484 ◽  
Author(s):  
J. Równicka-Zubik ◽  
A. Sułkowska ◽  
M. Dubas ◽  
J. Pożycka ◽  
M. Maciążek-Jurczyk ◽  
...  
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Binding Sites ◽  
Surface Hydrophobicity

Nof2206Probing the interaction of memantine, an important Alzheimer's drug, with human serum albumin: In silico and In vitro approach

2021 ◽  
pp. 116888
Author(s):  
Fahad A. Alhumaydhi ◽  
Mohammad Abdullah Aljasir ◽  
Abdullah S.M. Aljohani ◽  
Suliman A. Alsagaby ◽  
Ameen S.S. Alwashmi ◽  
...  
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
In Silico

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 Synthesis and In Vitro Assessment of pH-Sensitive Human Serum Albumin Conjugates of Pirarubicin

2020 ◽  
Vol 14 (1) ◽  
pp. 22
Author(s):  
Kenji Tsukigawa ◽  
Shuhei Imoto ◽  
Keishi Yamasaki ◽  
Koji Nishi ◽  
Toshihiko Tsutsumi ◽  
...  
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Coupling Reaction ◽  
Synthetic Polymer ◽  
Ph Sensitive ◽  
Acidic Ph ◽  
Polymer Conjugate ◽  
Acidic Conditions

In a previous study, we reported on the development of a synthetic polymer conjugate of pirarubicin (THP) that was formed via an acid-labile hydrazone bond between the polymer and the THP. However, the synthetic polymer itself was non-biodegradable, which could lead to unexpected adverse effects. Human serum albumin (HSA), which has a high biocompatibility and good biodegradability, is also a potent carrier for delivering antitumor drugs. The objective of this study was to develop pH-sensitive HSA conjugates of THP (HSA-THP), and investigate the release of THP and the cytotoxicity under acidic conditions in vitro for further clinical development. HSA-THP was synthesized by conjugating maleimide hydrazone derivatives of THP with poly-thiolated HSA using 2-iminothiolane, via a thiol-maleimide coupling reaction. We synthesized two types of HSA-THP that contained different amounts of THP (HSA-THP2 and HSA-THP4). Free THP was released from both of the HSA conjugates more rapidly at an acidic pH, and the rates of release for HSA-THP2 and HSA-THP4 were similar. Moreover, both HSA-THPs exhibited a higher cytotoxicity at acidic pH than at neutral pH, which is consistent with the effective liberation of free THP under acidic conditions. These findings suggest that these types of HSA-THPs are promising candidates for further development.

The in Vitro Anti-HIV Efficacy of Negatively Charged Human Serum Albumin Is Antagonized by Heparin

1997 ◽  
Vol 13 (8) ◽  
pp. 677-683 ◽  
Author(s):  
P.J. SWART ◽  
C.S. SUN ◽  
M.E. KUIPERS ◽  
C. ASUNCION ◽  
S. JOSEPHS ◽  
...  
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Anti Hiv

Zinc–human serum albumin association: testimony of two binding sites

Talanta ◽  
2004 ◽  
Vol 63 (2) ◽  
pp. 503-508 ◽  
Author(s):  
C. André ◽  
Y.C. Guillaume
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Binding Sites

scholarly journals Kinetic study of the photochemical changes of (ZZ)-bilirubin IX α bound to human serum albumin. Demonstration of (EZ)-bilirubin IX α as an intermediate in photochemical changes from (ZZ)-bilirubin IX α to (EZ)-cyclobilirubin IX α

1985 ◽  
Vol 226 (1) ◽  
pp. 251-258 ◽  
Author(s):  
S Itoh ◽  
S Onishi
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Kinetic Study ◽  
Human Serum ◽  
Photochemical Reaction ◽  
Relative Rate ◽  
Significant Preference ◽  
Geometrical Isomers ◽  
Relative Rate Constants

The present study was performed to elucidate why the photochemical reaction of (ZZ)-bilirubin bound to human serum albumin is singularly selective, and only one of the two (EZ)- and (ZE)-bilirubins, the (ZE)-isomer, is produced. In a kinetic study of the photochemical reaction in vitro, the sum of the relative rate constants of photochemical transformation of (EZ)-bilirubin into both (EZ)-cyclobilirubin and (ZZ)-bilirubin, with a significant preference for the former, was proved to be considerably larger than that of the transformation of (ZZ)-bilirubin into (EZ)-bilirubin. Therefore only one of the geometrical isomers, namely (ZE)-bilirubin, is apparently formed. It was concluded that (EZ)-bilirubin photochemically undergoes (EZ)-cyclization, i.e. structural photoisomerization, while bound to its high-affinity site on human serum albumin, and is an intermediate in the transformation of (ZZ)-bilirubin into (EZ)-cyclobilirubin.

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