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Unnatural Amino Acid Incorporation into Virus-Like Particles

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journal contribution
posted on 16.04.2008, 00:00 by Erica Strable, Duane E. Prasuhn, Andrew K. Udit, Steven Brown, A. James Link, John T. Ngo, Gabriel Lander, Joel Quispe, Clinton S. Potter, Bridget Carragher, David A. Tirrell, M. G. Finn
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.

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