Site-specific targeting of enterovirus capsid by functionalized monodisperse gold nanoclusters.
Development of precise protocols for accurate site-specific conjugation of monodisperse inorganic nanoparticles to biological material is one of the challenges in contemporary bionanoscience and nanomedicine. We report here a successful site-specific covalent conjugation of functionalized atomically monodisperse gold clusters with 1.5-nm metal cores to viral surfaces. Water-soluble Au102(para-mercaptobenzoic acid)44 clusters, functionalized by maleimide linkers to target cysteines of viral capsid proteins, were synthesized and conjugated to enteroviruses echovirus 1 and coxsackievirus B3. Quantitative analysis of transmission electron microscopy images and the known virus structures showed high affinity and mutual ordering of the bound gold clusters on the viral surface and a clear correlation between the clusters and the targeted cysteine sites close to the viral surface. Infectivity of the viruses was not compromised by loading of several tens of gold clusters per virus. These advances allow for future investigations of the structure-function relations of enteroviruses and enterovirus-related virus-like particles, including their entry mechanisms into cells and uncoating in cellular endosomes.
Departments of Biology and Environmental Science, Chemistry, and Physics, and Nanoscience Center, University of Jyväskylä, FI-40014 Jyväskylä, Finland.
Varpu
V
Marjomäki
Tanja
T
Lahtinen
Mari
M
Martikainen
Jaakko
J
Koivisto
Sami
S
Malola
Kirsi
K
Salorinne
Mika
M
Pettersson
Hannu
H
Häkkinen
D002213:Capsid; D002460:Cell Line; D004770:Enterovirus / Q000502:physiology* / Q000648:ultrastructure; D006046:Gold / Q000737:chemistry*; D053768:Metal Nanoparticles; D046529:Microscopy, Electron, Transmission
D006046:Gold
biolabeling; monolayer-protected cluster; virus tracking