Paclitaxel inhibited lysozyme fibrillation by increasing colloidal stability through formation of “off-pathway” oligomers

8Citations
Citations of this article
20Readers
Mendeley users who have this article in their library.
Get full text

Abstract

Protein fibrillation is a challenging issue in medicine, causing many diseases, and an impediment to pharmaceutics and protein industry. Many chemicals, especially polyphenol compounds and aromatic small molecules, have been widely used as an effective strategy to combat protein fibril formation. Hence, understanding mechanisms of fibrillation inhibition and contributing forces in this process are significant. In this study, the inhibitory effect of paclitaxel on lysozyme fibrillation was investigated with respect to thermal and colloidal stability. Fibrillation was monitored with ThT fluorescence, circular dichroism, and AFM; paclitaxel-lysozyme interaction with isothermal titration calorimetry and docking; thermal and colloidal stability with differential scanning calorimetry and zeta-pulse, respectively. Paclitaxel inhibited lysozyme fibrillation, and interacted with lysozyme through hydrogen bonds and van der Waals’ interactions. The viability of PC12 cells retrieved as a result of fibrillation inhibition by paclitaxel. Hydrophobic forces dominantly shielded the aggregation-prone region of lysozyme and suppressed the effective interactions between lysozyme monomers. Although paclitaxel did not affect lysozyme's thermal stability, it increased lysozyme's colloidal stability by either increasing the surface charge density or charge distribution on lysozyme. In conclusion, our results suggest a model for paclitaxel's inhibitory role through two complementary steps driving to “off-pathway” oligomer formation and attenuation of fibril formation.

Cite

CITATION STYLE

APA

Kachooei, E., Mozaffarian, F., Khodagholi, F., Sadeghi, P., Karami, L., Ghasemi, A., … Moosavi-Movahedi, A. A. (2018). Paclitaxel inhibited lysozyme fibrillation by increasing colloidal stability through formation of “off-pathway” oligomers. International Journal of Biological Macromolecules, 111, 870–879. https://doi.org/10.1016/j.ijbiomac.2018.01.072

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free