Temperature dependence of Congo red binding to amyloid β12-28. 2013

Ruel E McKnight, and Douglas R Jackson, and Kazushige Yokoyama
Department of Chemistry, State University of New York, College at Geneseo, Geneseo, NY, 14454, USA. mcknight@geneseo.edu

Because Congo red (CR) can bind to critical intermediate structural forms of amyloid beta (Aβ), it has been suggested as a potential therapeutic agent against neurodegenerative disorders such as Alzheimer's disease. In this study, the interaction of CR with Aβ(12-28) was investigated by use of isothermal titration calorimetry (ITC). Studies conducted between 15 and 35 °C show that binding of CR to Aβ(12-28) was strongly dependent on temperature, with a decrease in CR-Aβ(12-28) complexation as temperature increases, presumably because of conformational changes within Aβ(12-28) at the highest temperatures, that conceal the CR binding sites. In fact, no CR binding was observed at 35 °C. The binding of CR to Aβ(12-28) was associated with favorable changes in both enthalpy and entropy that resulted in binding constants (K) of between 10(5) and 10(6) M (-1). An early (and more intense) entropy-driven CR disaggregation phase (K ~10(7)-10(8) M (-1)) was observed before the onset of CR-Aβ(12-28) complexation. Only CR disaggregation was observed at 35 °C. These results may provide further insights into the ability of CR to inhibit Aβ toxicity in neurodegenerative diseases.

UI MeSH Term Description Entries
D008956 Models, Chemical Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment. Chemical Models,Chemical Model,Model, Chemical
D009682 Magnetic Resonance Spectroscopy Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING). In Vivo NMR Spectroscopy,MR Spectroscopy,Magnetic Resonance,NMR Spectroscopy,NMR Spectroscopy, In Vivo,Nuclear Magnetic Resonance,Spectroscopy, Magnetic Resonance,Spectroscopy, NMR,Spectroscopy, Nuclear Magnetic Resonance,Magnetic Resonance Spectroscopies,Magnetic Resonance, Nuclear,NMR Spectroscopies,Resonance Spectroscopy, Magnetic,Resonance, Magnetic,Resonance, Nuclear Magnetic,Spectroscopies, NMR,Spectroscopy, MR
D010446 Peptide Fragments Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques. Peptide Fragment,Fragment, Peptide,Fragments, Peptide
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D011487 Protein Conformation The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). Conformation, Protein,Conformations, Protein,Protein Conformations
D002021 Buffers A chemical system that functions to control the levels of specific ions in solution. When the level of hydrogen ion in solution is controlled the system is called a pH buffer. Buffer
D002151 Calorimetry The measurement of the quantity of heat involved in various processes, such as chemical reactions, changes of state, and formations of solutions, or in the determination of the heat capacities of substances. The fundamental unit of measurement is the joule or the calorie (4.184 joules). (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
D002942 Circular Dichroism A change from planar to elliptic polarization when an initially plane-polarized light wave traverses an optically active medium. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Circular Dichroism, Vibrational,Dichroism, Circular,Vibrational Circular Dichroism
D003224 Congo Red An acid dye used in testing for hydrochloric acid in gastric contents. It is also used histologically to test for AMYLOIDOSIS. Red, Congo
D006863 Hydrogen-Ion Concentration The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH pH,Concentration, Hydrogen-Ion,Concentrations, Hydrogen-Ion,Hydrogen Ion Concentration,Hydrogen-Ion Concentrations

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