X-ray and Electron Diffraction Observations of Steric Zipper Interactions in Metal-Induced Peptide Cross-β Nanostructures

The steric zipper is a common hydrophobic packing structureofpeptide side chains that forms between two adjacent & beta;-sheetlayers in amyloid and related fibrils. Although previous studies haverevealed that peptide fragments derived from native protein sequencesexhibit steric zipper structures, their de novo designs have rarelybeen studied. Herein, steric zipper structures were artificially constructedin the crystalline state by metal-induced folding and assembly oftetrapeptide fragments Boc-3pa-X-1-3pa-X-2-OMe(3pa: & beta;-(3-pyridyl)-l-alanine; X-1 and X-2: hydrophobic amino acids). Crystallographic studies revealedtwo types of packing structures, interdigitation and hydrophobic contact,that result in a class 1 steric zipper geometry when the X-1 and X-2 residues contain alkyl side chains. Furthermore,a class 3 steric zipper geometry was also observed for the first timeamong any reported steric zippers when using tetrapeptide fragmentswith (X-1, X-2) = (Thr, Thr) and (Phe, Leu). Thesystem could also be extended to a knob-hole-type zipper usinga pentapeptide sequence.