Amphiphilic peptide-polymer conjugates with side-conjugation.

Polymers conjugated to the exterior of a protein mediate its interactions with surroundings, enhance its processability and can be used to direct its macroscopic assemblies. Most studies to date have focused on peptide-polymer conjugates based on hydrophilic polymers. Engineering amphiphilicity into protein motifs by covalently linking hydrophobic polymers has the potential to interface peptides and proteins with synthetic polymers, organic solvents, and lipids to fabricate functional hybrid materials. Here, we synthesized amphiphilic peptide-polymer conjugates in which a hydrophobic polymer is conjugated to the exterior of a heme-binding four-helix bundle and systematically investigated the effects of the hydrophobicity of the conjugated polymer on the peptide structure and the integrity of the heme-binding pocket. In aqueous solution with surfactants present, the side-conjugated hydrophobic polymers unfold peptides and may induce an α-helix to β-sheet conformational transition. These effects decrease as the polymer becomes less hydrophobic and directly correlate with the polymer hydrophobicity. Upon adding organic solvent to solubilize the hydrophobic polymers, however, the deleterious effects of hydrophobic polymers on the peptide structures can be eliminated. Present studies demonstrate that protein structure is sensitive to the local environment. It is feasible to dissolve amphiphilic peptide-polymer conjugates in organic solvents to enhance their solution processability while maintaining the protein structures.