beta-Sheet to Helical-Sheet Evolution Induced by Topochemical Polymerization: Cross-alpha-Amyloid-like Packing in a Pseudoprotein with Gly-Phe-Gly Repeats

摘要

Protein-mimics are of great interest for their structure, stability, and properties. We are interested in the synthesis of protein-mimics containing triazole linkages as peptide-bond surrogate by topochemical azide-alkyne cycloaddition (TAAC) polymerization of azide- and alkyne-modified peptides. The rationally designed dipeptide N-3-CH2CO-Phe-NHCH2CCH (1) crystallized in a parallel beta-sheet arrangement and are head-to-tail aligned in a direction perpendicular to the beta-sheet-direction. Upon heating, crystals of 1 underwent single-crystal-to-single-crystal polymerization forming a triazole-linked pseudoprotein with Gly-Phe-Gly repeats. During TAAC polymerization, the pseudoprotein evolved as helical chains. These helical chains are laterally assembled by backbone hydrogen bonding in a direction perpendicular to the helical axis to form helical sheets. This interesting helical-sheet orientation in the crystal resembles the cross-alpha-amyloids, where alpha-helices are arranged laterally as sheets.