Formation of giant amphiphiles by post-functionalization of hydrophilic protein–polymer conjugates

A novel, generic method for the synthesis of families of tri-block protein–polymer giant amphiphiles was designed and developed. We have synthesized a hydrophilic α-maleimido poly-1-alkyne with Mn = 9.5 kDa (1H-NMR) and narrow PDi (1.15 as measured by SEC) via ATRP (Atom Transfer Radical Polymerization). This polymer was succesfully coupled to BSA to afford a hydrophilic multifunctional bioconjugate which was isolated using protein purification techniques and fully characterized. Following the post-functionalization approach, we introduced hydrophobicity to the resulting hydrophilic biohybrid by a straightforward, high yield “click”-chemistry cycloaddition step. The resulting tri-block protein–polymer amphiphiles were isolated and showed interesting aggregation patterns (TEM, confocal microscopy).