Associate Professor of Chemistry
University of Rochester
Rippled β-Sheets from Sequence Mismatched L- and D- Amphipathic Peptides
Rippled β-sheets are an emerging class of multicomponent supramolecular peptide biomaterial composed of enantiomeric L- and D-β-sheet peptides that coassemble in an alternating L/D pattern. While there have been several recent reports of rippled β-sheet formation from equimolar mixtures of enantiomeric L- and D-peptides, the potential for a broader spectrum of rippled β-sheet assemblies in which the L- and D- coassembly partners are not only of opposite chirality but also differ in amino acid sequence has not yet been explored. We hypothesized that mismatched L- and D- amphipathic peptides that differ in hydrophobic amino acid identity would preferentially coassemble into two-component rippled β-sheets.
Herein, we confirm this hypothesis by demonstrating the formation of rippled β-sheets from the coassembly of sequence mismatched L- and D- amphipathic Ac-(FKFE)2-NH¬2 and Ac-(VKVE)2-NH¬2 peptides. Mismatched coassembly of opposite chirality peptides results in peptide nanofibrils which are morphologically distinct from one-component pleated β-sheet fibrils or rippled β-sheet assemblies of the parent enantiomers.
Data is consistent with the formation of rippled β-sheet structures in which the L- and D- peptides are arranged in alternating fashion with high fidelity. This demonstration of rippled β-sheet coassembly between sequence mismatched amphipathic peptides of opposite chirality dramatically broadens the scope of these multicomponent assemblies as rationally designed next-generation biomaterials.