Title
Probing the role of ortho-dihydroxy groups on lysozyme fibrillation
Author
Mouli Konar, Debanjali Ghosh, Pritam Roy, Swagata Dasgupta
Year
2018
Journal
International Journal of Biological Macromolecules
Abstract
Changes in the microenvironment of Trp in lysozyme are one of the key factors in the fibrillation process. Gallic acid through the oxidation of o-dhydroxy moiety into quinone was shown to inhibit lysozyme fibrillation by stabilizing the Trp microregions [Konar et al., Int. J. Biol. Macromol. 103 (2017) 1224–1231]. In this article we compare the inhibitory effects of several gallic acid-based phenolic compounds. The results show that pyrogallol, and 3,4-dihydroxy benzoic acid, each containing the o-dihydroxy moiety exhibited a significant inhibitory effect on lysozyme fibrillation which is further supported by docking studies. Interestingly, the inhibitory effect of pyrogallol is almost similar to that observed for gallic acid. The lower inhibitory effect of 3,5-dihydroxy benzoic acid and 4-hydroxy benzoic acid corroborates this finding as neither of the compounds can be transformed into quinone intermediates. The ineffectiveness of benzoic acid towards fibrillation questions the role of the COOH group in the inhibition. The IC20 values determined show the similar trends. Results of the Thioflavin T binding assay and parameters from the docking studies reveal a strong correlation based on which a relation has been obtained that could be used to identify potential polyphenol based inhibitors by considering docking studies alone.
Instrument
J-815
Keywords
Circular dichroism, Secondary structure, Chemical stability, Aggregation, Biochemistry