Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 111, 870-879

Paclitaxel Inhibited Lysozyme Fibrillation by Increasing Colloidal Stability Through Formation of "Off-Pathway" Oligomers

Affiliations

Paclitaxel Inhibited Lysozyme Fibrillation by Increasing Colloidal Stability Through Formation of "Off-Pathway" Oligomers

Ehsan Kachooei et al. Int J Biol Macromol.

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.

Keywords: Amyloid; Calorimetry; Polyphenol; Thermal stability; Zeta potential.

Similar articles

See all similar articles

LinkOut - more resources

Feedback