• block copolymers;
  • radical polymerization;
  • micelles;
  • multifunctional block copolymers;
  • peptide conjugates;
  • reversible addition fragmentation chain transfer (RAFT)


Thumbnail image of graphical abstract

The synthesis of amphiphilic ABC-triblock peptide-polymer conjugates comprising a central oligopeptide segment and terminal hydrophilic poly(ethylene oxide) (PEO) as well as hydrophobic poly(butyl acrylate) (PBA) blocks is described. In aqueous solution, the amphiphilic segments of these functional conjugates direct the self-assembly into block copolymer micelles, while the functional oligopeptide is positioned at the hydrophilic and hydrophobic interface. For that the conjugate PEO-Arg10 was synthesized using solid-phase supported peptide synthesis techniques (SPPS). The supported precursor conjugate was functionalized at the amino-terminus of the peptide segment with a chain-transfer moiety for RAFT polymerization. Subsequently, the AB macro-CTA was liberated from the support and used to polymerize BA homogenously in solution. The RAFT radical polymerization process allowed controlling the molecular weight of the PBA-block, leading to amphiphilic ABC-conjugates with low polydispersities. The triblock peptide-polymer conjugate assembles in water into micellar aggregates, as was shown by light scattering and AFM. The molecular architecture of the ABC-triblock conjugate controls the positioning of the functional but expensive oligopeptide-segment within the aggregates, while the inexpensive synthetic polymer blocks are determining the aggregation behavior. Considering the design of the conjugate, the central Arg10 segment can be expected to be positioned at the interface between the hydrophobic and the hydrophilic polymer blocks, resulting in the formation of a functional domain with precisely controllable functionalities.