期刊
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
卷 111, 期 -, 页码 870-879出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijbiomac.2018.01.072
关键词
Amyloid; Polyphenol; Calorimetry; Thermal stability; Zeta potential
资金
- University of Tehran, Center of Excellence in Biothermodynamics (CEBiotherm)
- Iran National Science Foundation (INSF)
- Iran National Elites Foundation (INEF)
- Iran Society of Biophysical Chemistry
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 paditaxel 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. (C) 2018 Elsevier B.V. All rights reserved.
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