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Addressing Mechanism of Fibrillization/Aggregation and Its Prevention in Presence of Osmolytes: Spectroscopic and Calorimetric Approach

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Title Addressing Mechanism of Fibrillization/Aggregation and Its Prevention in Presence of Osmolytes: Spectroscopic and Calorimetric Approach
 
Creator CHOUDHARY, S
KISHORE, N
 
Subject THIOFLAVIN T-BINDING
PROTEIN AGGREGATION
AMYLOID FIBRILS
IN-VITRO
ALPHA-SYNUCLEIN
PRION PROTEIN
LYSOZYME
FIBRILLATION
INHIBITION
STABILITY
 
Description Understanding the mechanism of protein fibrillization/aggregation and its prevention is the basis of development of therapeutic strategies for amyloidosis. An attempt has been made to understand the nature of interactions of osmolytes L-proline, 4-hydroxy-L-proline, sarcosine and trimethylamine N-oxide with the different stages of fibrillization of hen egg-white lysozyme by using a combination of isothermal titration calorimetry, differential scanning calorimetry, fluorescence spectroscopy, and transmission electron microscopy. Based on thioflavin T fluorescence emission intensities and microscopic images, the nucleation, elongation, and saturation phases of fibrillization have been identified. Isothermal titration calorimetry and differential scanning calorimetry have enabled a quantitative analysis of the nature of interactions of these osmolytes with various conformational states of lysozyme at different stages of fibrillization/aggregation. It is concluded that interaction of the osmolytes with lysozyme fibrils at both the nucleation and elongation stages are important steps in the prevention of fibrillization/aggregation. Identification of the nature of interactions is a key step towards the discovery and synthesis of target oriented potential inhibitors of these associations. This study is a first report in which calorimetry has been used to address interaction of potential inihibitiors with the protein at different stages of fibrillization.
 
Publisher PUBLIC LIBRARY SCIENCE
 
Date 2014-12-29T06:31:00Z
2014-12-29T06:31:00Z
2014
 
Type Article
 
Identifier PLOS ONE, 9(8)
1932-6203
http://dx.doi.org/10.1371/journal.pone.0104600
http://dspace.library.iitb.ac.in/jspui/handle/100/17315
 
Language English