Title
Protein–Drug Nanoconjugates: Finding the alternative proteins as drug carrier
Author
Iqra Munir, Sadia Ajmal, Muhammad Raza Shah, Aftab Ahmad, Abdul Hameed, Syed Abid Ali
Year
2017
Journal
International Journal of Biological Macromolecules
Abstract
Present study was conducted to establish the interaction of bovine fetuin-A to validate its binding modalities with doxorubicin (Dox). Fetuin-A was purified to highest purity and monodispersity. Green synthesis of fetuin-A conjugated gold nanoparticles (F-GNPs) have been performed giving typical UV-maxima with subtle variation in fourier transform infrared spectroscopy (FTIR). Atomic force microscopy (AFM) revealed spherical shaped, polydisperse F-GNPs of varying sizes, complementing the radius of hydration (19.5-62.4 nm) by dynamic light scattering (DLS). Circular dichroism (CD) analysis of fetuin-A with respect to Dox interaction shows remarkable reduction in ellipticity with increasing concentrations of Dox (20–120 μM). Fetuin-A:Dox and F-GNPs:Dox at variable concentrations revealed significantly enhanced absorption spectra, while a continuous decrease in florescence (560 nm). This effect was more drastic when Dox interact with fetuin-A as compared to F-GNPs. Some known antimicrobial drugs were also investigated under similar conditions, giving strong quenching effect in a dose dependent manner suggesting the significant yet differential interactions. In cytotoxicity assay, fetuin-A:Dox conjugates revealed less toxicity as compared to F-GNPs:Dox and Dox alone. In-silico studies of the fetuin-A:Dox complex suggest that the drug binds in the major grove between beta-sheet and long loop region of D1 domain and stabilized by several hydrogen bonds.
Instrument
J-810
Keywords
Circular dichroism, Secondary structure, Biochemistry