Programmed and Sequential Disassembly of Multi‐Responsive Supramolecular Protein Nanoassemblies: A Detailed Mechanistic Investigation

Abstract

We report a novel chemical method for the construction of multi‐responsive supramolecular nanoassemblies using custom‐designed facially amphiphilic monodisperse protein‐dendron bioconjugates. The macromolecular synthons contain a globular hydrophilic protein domain site‐specifically conjugated to photo‐responsive hydrophobic benzyl‐ether dendron of different generations using oligoethylene glycol linkers of defined length. The size of the protein nanoassemblies can be systematically tuned by choosing an appropriate dendron or linker of defined length. Exposure of protein nanoassemblies to light results in partial disassembly of complex rather than complete disassembly. The newly formed protein nanoparticle no longer responds to light but could be disassembled into constitutive monomers at the acidic condition or further treatment with a small molecule. More interestingly, the distribution ratio of assembled versus disassembled states of protein nanoassemblies after photochemical reaction does not depend on the dendron generation or nature of linker functionality or the identity of the protein, but heavily influenced by choice of linker length. Altogether, this work discloses a new chemical method for the rational design of a monodisperse multi‐responsive protein‐based supramolecular system with exquisite control over the disassembly process.