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Functionalisation of Polyvinylpyrrolidone on Gold Nanoparticles Enhances Its Anti-Amyloidogenic Propensity towards Hen Egg White Lysozyme.

ABSTRACT: Protein amyloids are characterized by aggregates that usually consist of fibres containing misfolded proteins and having a cross ?-sheet conformation. These aggregates can eventually lead to several degenerative diseases like Alzheimer's disease, amyotrophic lateral sclerosis (ALS), Huntington's disease and Parkinson's disease. The present study describes the effect of chemically synthesized polyvinylpyrrolidone (PVP)-conjugated gold nanoparticles (PVP-AuNps) on hen egg white lysozyme (HEWL) amyloids. The synthesized nanoparticles have been characterized using various biophysical techniques like Ultraviolet-Visible (UV-Vis) Spectroscopy, Transmission electron microscopy (TEM), X-ray diffraction (XRD) analysis, dynamic light scattering (DLS), zeta-potential measurement and Fourier transform infrared spectroscopy (FTIR). The aggregation studies showed that PVP acts as a partial inhibitor of HEWL amyloidogenesis. However, when conjugated to gold nanoparticle surface, it leads to complete inhibition of amyloid formation. Apart from inhibition, PVP-conjugated gold nanoparticles also exhibited a significant disaggregation effect on mature amyloids and hence can be exploited as an effective therapeutic agent against hereditary systemic amyloidosis.

SUBMITTER: Das T

PROVIDER: S-EPMC5489805 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Functionalisation of Polyvinylpyrrolidone on Gold Nanoparticles Enhances Its Anti-Amyloidogenic Propensity towards Hen Egg White Lysozyme.

Das Tulika T Kolli Vidyalatha V Karmakar Srijeeb S Sarkar Nandini N

Biomedicines 20170503 2

Protein amyloids are characterized by aggregates that usually consist of fibres containing misfolded proteins and having a cross β-sheet conformation. These aggregates can eventually lead to several degenerative diseases like Alzheimer's disease, amyotrophic lateral sclerosis (ALS), Huntington's disease and Parkinson's disease. The present study describes the effect of chemically synthesized polyvinylpyrrolidone (PVP)-conjugated gold nanoparticles (PVP-AuNps) on hen egg white lysozyme (HEWL) amy ...[more]

PMID: 28536362

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Project description:Chemical bonding at the active site of hen egg-white lysozyme (HEWL) is analyzed on the basis of Bader's quantum theory of atoms in molecules [QTAIM; Bader (1994), Atoms in Molecules: A Quantum Theory. Oxford University Press] applied to electron-density maps derived from a multipole model. The observation is made that the atomic displacement parameters (ADPs) of HEWL at a temperature of 100?K are larger than ADPs in crystals of small biological molecules at 298?K. This feature shows that the ADPs in the cold crystals of HEWL reflect frozen-in disorder rather than thermal vibrations of the atoms. Directly generalizing the results of multipole studies on small-molecule crystals, the important consequence for electron-density analysis of protein crystals is that multipole parameters cannot be independently varied in a meaningful way in structure refinements. Instead, a multipole model for HEWL has been developed by refinement of atomic coordinates and ADPs against the X-ray diffraction data of Wang and coworkers [Wang et al. (2007), Acta Cryst. D63, 1254-1268], while multipole parameters were fixed to the values for transferable multipole parameters from the ELMAM2 database [Domagala et al. (2012), Acta Cryst. A68, 337-351] . Static and dynamic electron densities based on this multipole model are presented. Analysis of their topological properties according to the QTAIM shows that the covalent bonds possess similar properties to the covalent bonds of small molecules. Hydrogen bonds of intermediate strength are identified for the Glu35 and Asp52 residues, which are considered to be essential parts of the active site of HEWL. Furthermore, a series of weak C-H...O hydrogen bonds are identified by means of the existence of bond critical points (BCPs) in the multipole electron density. It is proposed that these weak interactions might be important for defining the tertiary structure and activity of HEWL. The deprotonated state of Glu35 prevents a distinction between the Phillips and Koshland mechanisms.

Dataset Information

Functionalisation of Polyvinylpyrrolidone on Gold Nanoparticles Enhances Its Anti-Amyloidogenic Propensity towards Hen Egg White Lysozyme.

Publications

Functionalisation of Polyvinylpyrrolidone on Gold Nanoparticles Enhances Its Anti-Amyloidogenic Propensity towards Hen Egg White Lysozyme.

Similar Datasets

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