Published April 16, 2008 | Version Accepted Version + Supplemental Material
Journal Article Open

Unnatural Amino Acid Incorporation into Virus-Like Particles

Abstract

Virus-like particles composed of hepatitis B virus (HBV) or bacteriophage Qβ capsid proteins have been labeled with azide- or alkyne-containing unnatural amino acids by expression in a methionine auxotrophic strain of E. coli. The substitution does not affect the ability of the particles to self-assemble into icosahedral structures indistinguishable from native forms. The azide and alkyne groups were addressed by Cu(I)-catalyzed [3 + 2] cycloaddition: HBV particles were decomposed by the formation of more than 120 triazole linkages per capsid in a location-dependent manner, whereas Qβ suffered no such instability. The marriage of these well-known techniques of sense-codon reassignment and bioorthogonal chemical coupling provides the capability to construct polyvalent particles displaying a wide variety of functional groups with near-perfect control of spacing.

Additional Information

© 2008 American Chemical Society Received October 21, 2007; Revised Manuscript Received January 14, 2008 This work was supported by the NIH (AI056013, RR021886, GM62523), the David & Lucille Packard Foundation Interdisciplinary Science Program, and the Canadian Institutes of Health Research (postdoctoral fellowship to A.K.U.). Cryo-electron microscopy was performed at the National Resource for Automated Molecular Microscopy which is supported by the NIH NCRR P41 program (RR17573).

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Accepted Version - nihms-116689.pdf

Supplemental Material - bc700390r-file002.pdf

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Additional details

Identifiers

PMCID
PMC2713011
Eprint ID
53231
DOI
10.1021/bc700390r
Resolver ID
CaltechAUTHORS:20150107-082245467

Related works

Describes
10.1021/bc700390r (DOI)

Funding

NIH
AI056013
NIH
RR021886
NIH
GM62523
David and Lucile Packard Foundation
Canadian Institutes of Health Research
NIH
RR17573

Dates

Created
2015-01-07
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Updated
2021-11-10
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