Synthesis of Zwitterionic Diblock Copolymers with Cleavable Biotin Groups at the Junction Points and Fabrication of Bioconjugates by Biotin–Streptavidin Coupling

Abstract

Combinations of synthetic polymers and natural proteins provide a route to the synthesis of new biomaterials. The bioconjugates combining tunable properties of polymers with functionalities of proteins have found broad applications. One of the most challenging problems in this research field is the self-assembly behaviors of responsive polymer−protein bioconjugates. In this research, synthesis and self-assembly of bioconjugates composed of zwitterionic block copolymer and streptavidin were investigated. Block copolymers of poly(ethylene glycol) (PEG) and poly[3-dimethyl(methacryloyloxyethyl)ammonium propanesulfonate] (PDMAPS) with cleavable biotin groups at the junction points were synthesized. The zwitterionic block copolymers exhibit phase transitions with upper critical solution temperatures (UCSTs) in aqueous solutions. The concentration of sodium chloride exerts a significant influence on the UCST. The zwitterionic block copolymer chains selfassemble into vesicles in aqueous solution at a temperature below UCST. Bioconjugates comprising of streptavidin molecules and zwitterionic block copolymer chains were fabricated based on biotin−streptavidin coupling. Upon conjugation to the protein molecules, the UCST of the zwitterionic block copolymer decreases due to the screening effect of the protein molecules. The bioconjugates are able to make self-assembly into different structures, depending on the average number of block copolymer chains on a protein molecule. The bioconjugate molecules with average 1.3 block copolymer chains on a streptavidin selfassemble into rodlike structures, while those with average 2.9 chains on a streptavidin self-assemble into spherical micelles.

Biomimetic Mineralization of Protein Nanogels for Enzyme Protection

“…We ando ther researchers have demonstrated that the conjugation of proteins to thermally responsivep olymers could change the phase-transition temperatures of the polymers significantly. [21][22][23][24] The shift in the phasetransition temperature of PNIPAM in PPL nanogelsi sa ttributed to the incorporation of PPL molecules to the network structures and an increase in the hydrophilicity of the polymer. After coating with BSA, the endotherm of PNIPAM shifts to the high-temperature regime.…”

Fabrication of Polymer–Protein Hybrids

“…More structures, such as rodlike structures, can be obtained by the self‐assembly approach. Our group described the synthesis and self‐assembly of bioconjugates composed of zwitterionic diblock copolymers with cleavable biotin and streptavidin ( Figure ) . A block copolymer of PEG and PDMAPS with cleavable biotin groups at the junction points (PEG‐ b ‐PDMAPSSSBiotin) was synthesized by a combination of click chemistry, thiol–disulfide exchange, and ATRP (Figure a).…”

“…TEM images of self‐assembled structures of c) streptavidin‐bp 1.3 and d) streptavidin‐bp 2.9 in water at room temperature. Reproduced with permission . Copyright 2017, American Chemical Society.…”

“…Our group described the synthesis and self-assembly of bioconjugates composed of zwitterionic diblock copolymers with cleavable biotin and streptavidin (Figure 7). [183] A block copolymer of PEG and PDMAPS with cleavable biotin groups at the junction points (PEG-b-PDMAPSSSBiotin) was synthesized by a combination of click chemistry, thiol-disulfide exchange, and ATRP (Figure 7a). The block copolymer was conjugated to streptavidin by streptavidin-biotin interaction.…”

Temperature and pH Controlled Self‐Assembly of a Protein–Polymer Biohybrid

“…Previous research focused on preparing bioconjugates were mainly based on proteins such as bovine serum albumin (BSA), ovalbumin, chymotrypsin, streptavidin, and green fluorescent protein . Hoffman and co‐workers carried out pioneering work on preparation of various protein–PNIPAm conjugates for regulation of enzyme activity, triggered release, and enzyme recovery .…”