Bioconjug Chem. 2019 Jun 19;30(6):1636-1641. doi: 10.1021/acs.bioconjchem.9b00327. Epub 2019 Jun 5.
Capsid of tomato bushy stunt virus consists of an outer coat protein shell decorated on an internal skeleton comprising a β-annulus motif. We mimicked this capsid structure with our artificial viral capsid dressed up with protein. We synthesized the β-annulus peptide bearing a Cys at the C-terminal side and linked it with Cys34 of the human serum albumin (HSA) via a bismaleimide linker. The β-annulus peptide-HSA conjugate self-assembled into spherical structures of a 50-70 nm size range in the Tris-HCl buffer, with the ζ-potential of assemblies of such conjugate revealing that HSA proteins were displayed on the outer surface of the artificial viral capsid. Interestingly, the critical aggregation concentration (CAC) of the conjugate in the Tris-HCl buffer at 25 °C was approximately 0.01 μM, or 1/2500 lower than that of the unmodified β-annulus peptides, suggesting that the artificial viral capsids were stabilized via HSA modification. The present strategy of constructing protein nanocapsule by self-assembly of a β-annulus peptide-protein conjugate is simpler than that of previously reported protein nanocapsules.
番茄丛矮病毒的衣壳由外部蛋白壳组成,内部骨架由β-环糊精基序组成。我们用人工病毒衣壳模拟了这种结构,用蛋白进行了修饰。我们合成了带有 C 末端半胱氨酸的β-环糊精肽,并通过双马来酰亚胺接头将其与人血清白蛋白(HSA)的 Cys34 连接。β-环糊精肽-HSA 缀合物在 Tris-HCl 缓冲液中自组装成 50-70nm 大小范围的球形结构,该缀合物组装体的 ζ-电势表明 HSA 蛋白被展示在人工病毒衣壳的外表面。有趣的是,该缀合物在 25°C 的 Tris-HCl 缓冲液中的临界聚集浓度(CAC)约为 0.01 μM,比未修饰的β-环糊精肽低约 1/2500,表明通过 HSA 修饰稳定了人工病毒衣壳。与之前报道的蛋白纳米胶囊相比,通过β-环糊精肽-蛋白缀合物自组装构建蛋白纳米胶囊的策略更为简单。