Artificial Viral Capsid Dressed Up with Human Serum Albumin

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.