Effects of Secondary Structures and pH on the Self-Assembly of Poly(ethylene glycol)--polytyrosine.

Different from conventional synthetic polymers, polypeptides exhibit a distinguishing characteristic of adopting specific secondary structures, including random coils, α-helixes, and β-sheets. The conformation determines the rigidity and solubility of polypeptide chains, which further direct the self-assembly and morphology of the nanostructures. We studied the effect of distinct secondary structures on the self-assembly behavior of polytyrosine (PTyr)-derived amphiphilic copolymers. Two block copolymers of enantiopure poly(ethylene glycol)--poly(l-tyrosine) (PEG--P(l-Tyr)) and racemic poly(ethylene glycol)--poly(dl-tyrosine) (PEG--P(dl-Tyr)) were synthesized through the ring-opening polymerization of l-tyrosine -thiocarboxyanhydride (l-Tyr-NTA) and dl-tyrosine -thiocarboxyanhydride (dl-Tyr-NTA), respectively, by using poly(ethylene glycol) amine as the initiator. PEG--P(l-Tyr) adopts a β-sheet conformation and self-assembles into rectangular nanosheets in aqueous solutions, while PEG--P(dl-Tyr) is primarily in a random coil conformation with a tiny content of β-sheet structures, which self-assembles into sheaf-like nanofibrils. A pH increase results in the ionization of phenolic hydroxyl groups, which decreases the β-sheet content and increases the random coil content of the PTyr segments. Accordingly, PEG--P(l-Tyr) and PEG--P(dl-Tyr) self-assemble to form slender nanobelts and twisted nanoribbons, respectively, in alkaline aqueous solutions. The secondary structure-driven self-assembly of PTyr-derived copolymers is promising to construct filamentous nanostructures, which have potential for applications in controlled drug release.