Unnatural amino acid incorporation into virus-like particles.
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.
Strable
Erica
E
Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037, USA.
Prasuhn
Duane E
DE
Udit
Andrew K
AK
Brown
Steven
S
Link
A James
AJ
Ngo
John T
JT
Lander
Gabriel
G
Quispe
Joel
J
Potter
Clinton S
CS
Carragher
Bridget
B
Tirrell
David A
DA
Finn
M G
MG
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
D000596:Amino Acids; D036022:Capsid Proteins; D014357:Trypsin