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

Abstract

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 N 3 ‐Leu‐Ala‐NH‐CH 2 ‐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.