Secondary Structure-Driven Self-Assembly of Thiol-Reactive Polypept(o)ides

Area of Science:

• Polymer Chemistry
• Materials Science
• Biotechnology

Background:

• Secondary structure formation (α-helices, β-sheets) is a key feature differentiating polypeptides from other synthetic polymers.
• These secondary structures offer an additional parameter to control self-assembly and nanostructure morphology.
• Reactive amphiphilic polypeptides enable core cross-linking for morphology preservation.

Purpose of the Study:

• To investigate the influence of distinct secondary structures on the self-assembly of reactive amphiphilic polypeptides.
• To explore how different secondary structures (α-helices, antiparallel β-sheets, disrupted β-sheets) affect nanostructure formation.
• To analyze the self-assembly behavior of specific thiol-responsive copolymers.

Main Methods:

• Synthesis of thiol-responsive copolymers: polysarcosine-block-poly(S-ethylsulfonyl-dl-cysteine) (pSar-b-p(dl)Cys), polysarcosine-block-poly(S-ethylsulfonyl-l-cysteine) (pSar-b-p(l)Cys), and polysarcosine-block-poly(S-ethylsulfonyl-l-homocysteine) (pSar-b-p(l)Hcy) via N-carboxyanhydride polymerization.
• Characterization of secondary structures using spectroscopic methods (implied).
• Nanoprecipitation to induce self-assembly.
• Morphological analysis using atomic force microscopy (AFM) and cryogenic transmission electron microscopy (cryo-TEM).

Main Results:

• Copolymers with antiparallel β-sheets exhibited the strongest self-assembly tendency upon nanoprecipitation.
• Copolymers with disrupted β-sheets showed minimal aggregation.
• Polypeptides with α-helices and antiparallel β-sheets formed distinct nanostructures, including worm-like micelles, spherical micelles, and ellipsoidal structures.
• Core cross-linking via disulfide bonds preserved the formed morphologies.

Conclusions:

• Secondary structure plays a crucial role in directing the self-assembly of synthetic polypeptides.
• The specific type of secondary structure (e.g., antiparallel β-sheets) significantly influences the resulting nanostructure morphology.
• Synthetic polypeptides offer a versatile platform for designing self-assembled nanostructures with controlled morphologies driven by secondary structure.