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

Abstract

Tuning the secondary structure of a protein or polymer in the solid-state is challenging. Here we report the topochemical synthesis of a pseudoprotein and its secondary structure tuning in the solid-state. We designed the dipeptide monomer N₃ -Leu-Ala-NH-CH₂ -C≡CH (1) for topochemical azide-alkyne cycloaddition (TAAC) polymerization. Dipeptide 1 adopts an anti-parallel β-sheet-like stacked arrangement in its crystals. Upon heating, the dipeptide undergoes quantitative TAAC polymerization in a crystal-to-crystal fashion yielding large polymers. The reaction occurs between the adjacent monomers in the H-bonded anti-parallel stack, yielding pseudoprotein having a β-meander structure. When dissolved in methanol, this pseudoprotein changes its secondary structure from β-meander to α-helical form and it retains the new secondary structure upon desolvation. This work demonstrates a novel paradigm for tuning the secondary structure of a polymer in the solid-state.

Keywords: azide-alkyne cycloaddition; motion in crystal; pseudoprotein; topochemical polymerization; α-helix.