Secondary structure drives self-assembly in weakly segregated globular protein-rod block copolymers*

Protein-polymer bioconjugates combine protein functionality with polymer material properties and block copolymer self-assembly. The effect of polymer block secondary structure and chirality on solution-state self-assembly was studied using bioconjugates with a globular protein block (enhanced green fluorescent protein, or eGFP) and a poly(amino acid) (PAA) block with varying chirality. Block copolymers were synthesized by NCA polymerization, followed by native chemical ligation to eGFP. Homochiral _L- and _D- type PAAs formed α-helices, while an achiral random copolymer of _L- and _D- type monomers was structureless. All bioconjugates with an α-helical block self-assembled into lamellae with similar phase diagrams regardless of chirality type. However, bioconjugates with an achiral block remained disordered at all concentrations and temperatures measured. This was due to a non-repulsive interaction between the flexible achiral PAA and eGFP. Thus, incorporation of secondary structure into the polymer block can increase the effective segregation strength between blocks and drive self-assembly even with weak to no repulsion between blocks.