title: Unnatural amino acid incorporation into virus-like particles.
abstract: Virus-like particles composed of hepatitis B virus (HBV) or bacteriophage Qbeta 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 Qbeta 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.
authors.affiliation: Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Erica
authors.initials: E
authors.lastname: Strable
authors.forename: Duane E
authors.initials: DE
authors.lastname: Prasuhn
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Udit
authors.forename: Steven
authors.initials: S
authors.lastname: Brown
authors.forename: A James
authors.initials: AJ
authors.lastname: Link
authors.forename: John T
authors.initials: JT
authors.lastname: Ngo
authors.forename: Gabriel
authors.initials: G
authors.lastname: Lander
authors.forename: Joel
authors.initials: J
authors.lastname: Quispe
authors.forename: Clinton S
authors.initials: CS
authors.lastname: Potter
authors.forename: Bridget
authors.initials: B
authors.lastname: Carragher
authors.forename: David A
authors.initials: DA
authors.lastname: Tirrell
authors.forename: M G
authors.initials: MG
authors.lastname: Finn
mesh_terms: D017908:Allolevivirus / Q000378:metabolism*; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000378:metabolism*; D036022:Capsid Proteins / Q000737:chemistry / Q000378:metabolism*; D019281:Dimerization; D006515:Hepatitis B virus / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020836:Protein Structure, Quaternary; D014357:Trypsin / Q000378:metabolism
chemical_list: D000596:Amino Acids; D036022:Capsid Proteins; D014357:Trypsin