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 alpha-maleimido poly-1-alkyne with M-n = 9.5 kDa (H-1-NMR) and narrow PDi (1.15 as measured by SEC) via ATRP (Atom Transfer Radical Polymerization). This polymer was successfully 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).