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Probing the non-covalent interaction of ultrasmall gold nanoparticles with selected proteins

Grant number: 19/06750-8
Support type:Regular Research Grants
Duration: September 01, 2020 - August 31, 2022
Field of knowledge:Physical Sciences and Mathematics - Physics - Condensed Matter Physics
Cooperation agreement: DAAD
Mobility Program: SPRINT - Projetos de pesquisa - Mobilidade
Principal Investigator:Cristiano Luis Pinto de Oliveira
Grantee:Cristiano Luis Pinto de Oliveira
Principal investigator abroad: Matthias Epple
Institution abroad: University of Duisburg-Essen, Essen, Germany
Home Institution: Instituto de Física (IF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Assoc. researchers:André Luiz Sehnem ; Antonio Martins Figueiredo Neto
Associated research grant:16/24531-3 - Structural and biophysics properties of native and modified lipoproteins, AP.TEM


The aim of the applying bilateral project between Germany and Brazil is to synthesize ultrasmall gold nanoparticles (usAu-nanoparticles) for a specific interaction with different proteins. This work will combine the complementary expertise of both groups in synthetic chemistry (University of Duisburg-Essen, UDE) and biophysics (University of São Paulo, USP). It involves a number of young researchers from both groups to enhance their experience in the complementary area of nanoscience. In the project, usAu-nanoparticles will be wet-chemically synthesized from tetrachloroauric acid (HAuCl4) and sodium borohydride (NaBH4) as reducing agent and surface-functionalized with organic ligands. The covalent attachment of smaller ligands (e.g. cysteine, glutathione, mercaptobenzoic acid) to the surface of nanoparticles is based on the strong Au-S-bond, whereas a covalent surface modification with alkyne-containing larger molecules (peptides, molecular tweezers, and synthetic macromolecules) will be possible by copper-catalyzed click chemistry. Besides the fundamental characterization of the nanoparticles, they will be prepared to selectively address epitopes on the protein surface with the following model proteins: Survivin, 14-3-3, hPin1, and taspase, which are also available in pure form. The details of the interaction between protein-specific nanoparticles and the mentioned proteins and the surface composition of the nanoparticles will be elucidated by small-angle X-ray scattering (SAXS), a special expertise of the Brazilian group, dynamic light scattering, NMR spectroscopy, and analytical disc centrifugation (DCS). The sizes obtained from scattering methods for the coated nanoparticles can be compared with the results from high-resolution transmission electron microscopy (HRTEM), which can give information about the thickness of the coating shell and the nature of the nanoparticle-protein interaction. As complimentary information, the overall size and shape of the investigated protein molecules will be also determined by SAXS solution studies. During the project, the nanoparticle-protein-interaction will be elucidated by high-end biophysical methods, in particular SAXS, which is not available at this level at the University of Duisburg-Essen. Additionally, the effects of multiavidity (two or more identical ligands on one nanoparticle) and heteroavidity (two or more different ligands on each nanoparticle) for protein targeting will be explored. (AU)