Peptide/protein-polymer conjugates make up a new class of soft matter comprising natural and synthetic building blocks. They have the potential to combine the advantages of proteins and synthetic polymers (i.e., the precise chemical structure and diverse functionalities of biomolecules and the stability and processability of synthetic polymers) to generate hybrid materials with properties yet to be realized with either component alone. Here we briefly discuss recent developments in the design, fundamental understanding, and self-assembly of various peptide-polymer conjugates, as well as emerging biological and nonbiological applications that range from nanomedicine, to separation, and beyond.

Generating stable, multi-functional organic nanocarriers will have a significant impact on drug formulation. However, it remains a significant challenge to generate organic nanocarriers with a long circulation half-life, effective tumor penetration and efficient clearance of metabolites. We have advanced this goal by designing a new family of amphiphiles based on coiled-coil 3-helix bundle forming peptide-poly(ethylene glycol) conjugates. The amphiphiles self-assemble into monodisperse micellar nanoparticles, 15 nm in diameter. Using the 3-helix micelles, a drug loading of ~8 wt% was obtained using doxorubicin (DOX) and the micelles showed minimal cargo leakage after 12 hours of incubation with serum proteins at 37°C. In vivo pharmacokinetics studies using positron emission tomography (PET) showed a circulation half-life of 29.5 hrs and minimal accumulation in the liver and spleen. The demonstrated strategy, by incorporating unique protein tertiary structure in the headgroup of an amphiphile, opens new avenues to generate organic nanoparticles with tunable stability, ligand clustering and controlled disassembly to meet current demands in nanomedicine.

We present a new design of peptide–polymer conjugates where a polymer chain is covalently linked to the side chain of a helix bundle-forming peptide. The effect of conjugated polymer chains on the peptide structure was examined using a de novo designed three-helix bundle and a photoactive four-helix bundle. Upon attachment of poly(ethylene glycol) to the exterior of the coiled-coil helix bundle, the peptide secondary structure was stabilized and the tertiary structure, that is, the coiled-coil helix bundle, was retained. When a heme-binding peptide as an example is used, the new peptide–polymer conjugate architecture also preserves the built-in functionalities within the interior of the helix bundle. It is expected that the conjugated polymer chains act to mediate the interactions between the helix bundle and its external environment. Thus, this new peptide–polymer conjugate design strategy may open new avenues to macroscopically assemble the helix bundles and may enable them to function in nonbiological environments.