Secondary Structure Tuning of a Pseudoprotein Between β-Meander and α-Helical Forms in the Solid-State

Area of Science:

• Polymer Chemistry
• Materials Science
• Biomaterials Science

Background:

• Controlling protein and polymer secondary structures in the solid-state presents significant challenges.
• Existing methods often lack precision or require solution-phase processing.

Purpose of the Study:

• To report the topochemical synthesis of a pseudoprotein with tunable solid-state secondary structure.
• To demonstrate a novel paradigm for solid-state polymer secondary structure manipulation.

Main Methods:

• Design and synthesis of a dipeptide monomer (N3-Leu-Ala-NH-CH2-C≡CH) for topochemical azide-alkyne cycloaddition (TAAC) polymerization.
• Crystal engineering of the monomer to adopt an anti-parallel β-sheet-like arrangement.
• Solid-state polymerization via crystal-to-crystal transformation upon heating.

Main Results:

• Quantitative TAAC polymerization occurred in a crystal-to-crystal manner, yielding polymers with a β-meander structure derived from the monomer's stacked arrangement.
• The synthesized pseudoprotein exhibited a reversible secondary structure transition from β-meander to α-helical upon dissolution in methanol.
• The α-helical structure was retained even after desolvation, demonstrating stable solid-state structure modification.

Conclusions:

• A novel topochemical polymerization strategy enables precise control over polymer secondary structures in the solid-state.
• This approach offers a new pathway for designing functional materials with tailored solid-state conformations.
• The ability to tune secondary structures post-synthesis opens avenues for advanced material design and applications.