Title
Inhibition of amyloid fibril formation of β-lactoglobulin by the natural and synthetic curcuminoids
Author
Sanhita Maity, Sampa Pal, Subrata Sardar, Nayim Sepay, Hasan Parvej, Shahnaz Begum, Ramkrishna Dalui, Niloy Das, Anirban Pradhan, Umesh Chandra Chandra Halder
Year
2018
Journal
New Journal of Chemistry
Abstract
The aggregation of proteins have been associated with several aspects of daily life, including food processing, blood coagulation and many neurodegenerative diseases. However, the actual mechanisms responsible for amyloidosis-the irreversible fibril formation of various proteins that is linked to disorders such as Alzheimer’s, Creutzfeldt-Jakob and Huntington’s diseases have not yet been fully elucidated. Curcumin, a potent anti-oxidant exhibits anti-amyloid activity but its activity is limited owing to its instability. Therefore, chemical modifications of curcumin have been performed to discover molecules with enhanced stability and superior anti-amyloid activity. Herein, main objective of this study related to the inhibitory effect of three stable analogs of curcumin against bovine β-lactoglobulin (β-lg) fibrillization. We inferred that pyrazole derivative of curcumin showed remarkable potency in arresting fibrillization of β-lg as revealed by some biophysical techniques. Molecular docking demonstrated that pyrazole mediated inhibition of β-lg fibrillogenesis may be initiated by interacting aggregation prone regions of protein and preventing interactions between monomers and leading to suppression of the overall aggregation process. This work would allude to possible broader scope for discovery of other small molecules that may exert similar effect against amyloid formation and its associated neurodegenerative disease.
Instrument
J-815
Keywords
Circular dichroism, Secondary structure, Chemical stability, Aggregation, Biochemistry