Structural characterization of site-modified nanocapsid with monodispersed gold clusters
Stark, M., Baikoghli, M. A., Lahtinen, T., Malola, S., Xing, L., Nguyen, M., Nguyen, M., Sikaroudi, A., Marjomäki, V., Häkkinen, H., & Cheng, H. (2017). Structural characterization of site-modified nanocapsid with monodispersed gold clusters. Scientific Reports, 7, Article 17048. https://doi.org/10.1038/s41598-017-17171-x
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Scientific ReportsAuthors
Xing, Li |
Date
2017Discipline
Solu- ja molekyylibiologiaFysikaalinen kemiaNanoscience CenterCell and Molecular BiologyPhysical ChemistryNanoscience CenterCopyright
© the Authors, 2017. This is an open access article licensed under a Creative Commons Attribution 4.0 International License.
Hepatitis E Virus-like particles self-assemble in to noninfectious nanocapsids that are resistant
to proteolytic/acidic mucosal delivery conditions. Previously, the nanocapsid was engineered to
specifcally bind and enter breast cancer cells, where successful tumor targeting was demonstrated
in animal models. In the present study, the nanocapsid surface was modifed with a solvent-exposed
cysteine to conjugate monolayer protected gold nanoclusters (AuNC). Unlike commercially available
gold nanoparticles, AuNCs monodisperse in water and are composed of a discrete number of gold
atoms, forming a crystalline gold core. Au102pMBA44 (Au102) was an ideal conjugate given its small
2.5nm size and detectability in cryoEM. Au102 was bound directly to nanocapsid surface cysteines via
direct ligand exchange. In addition, Au102 was functionalized with a maleimide linker (Au102_C6MI) for
maleimide-thiol conjugation to nanocapsid cysteines. The AuNC-bound nanocapsid constructs were
conjugated in various conditions. We found Au102_C6MI to bind nanocapsid more efciently, while Au102
remained more soluble over time. Nanocapsids conjugated to Au102_C6MI were imaged in cryoEM for
single particle reconstruction to localize AuNC position on the nanocapsid surface. We resolved fve
unique high intensity volumes that formed a ring-shaped density at the 5-fold symmetry center. This
fnding was further supported by independent rigid modeling.
...
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Nature Publishing GroupISSN Search the Publication Forum
2045-2322Publication in research information system
https://converis.jyu.fi/converis/portal/detail/Publication/27412256
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Research Council of FinlandFunding program(s)
Academy Project, AoFAdditional information about funding
We thank J. Koivisto, K. Salorinne, J. Noronha for characterization and preparation of gold nanoclusters and conjugation. We also thank Fei Guo for his technical support in obtaining Cryo Electron Microscopy images. This work has been funded by the Finland Distinguished Professor Program by TEKES (grant 1913/31/2012) and by the Academy of Finland (grant 266492 and Academy Professorship of H.H.), by the National Institute of Food and Agriculture and by the NIH (grants: AI095382, EB021230, CA198880) to RHC. ...License
Except where otherwise noted, this item's license is described as © the Authors, 2017. This is an open access article licensed under a Creative Commons Attribution 4.0 International License.
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