Strable Erica, Prasuhn Duane E, Udit Andrew K, Brown Steven, Link A James, Ngo John T, Lander Gabriel, Quispe Joel, Potter Clinton S, Carragher Bridget, Tirrell David A, Finn M G
Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037, USA.
Bioconjug Chem. 2008 Apr;19(4):866-75. doi: 10.1021/bc700390r. Epub 2008 Mar 5.
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.
由乙型肝炎病毒（HBV）或噬菌体Qβ衣壳蛋白组成的病毒样颗粒，已通过在大肠杆菌的甲硫氨酸营养缺陷型菌株中表达，用含叠氮化物或炔烃的非天然氨基酸进行了标记。这种取代并不影响颗粒自组装成与天然形式难以区分的二十面体结构的能力。叠氮化物和炔烃基团通过铜（I）催化的[3 + 2]环加成反应进行处理：HBV颗粒通过每个衣壳形成超过120个三唑键以位置依赖的方式分解，而Qβ则没有这种不稳定性。这些众所周知的义密码子重新分配和生物正交化学偶联技术的结合，提供了构建展示各种官能团的多价颗粒的能力，并且对间距具有近乎完美的控制。
