Charge‐Separated Fmoc‐Peptide β‐Sheets: Sequence‐Secondary Structure Relationship for Arranging Charged Side Chains on Both Sides

Abstract β‐Sheet formation from fluorenylmethoxycarbonyl (Fmoc)‐substituted polar oligopeptides was demonstrated, where acidic and basic side chains are located separately on either side of the β‐sheet surfaces. For yielding such charge‐separated β‐sheets, self‐assembly of 18 pentapeptides was studied, all of which contain glutamic acid (E), lysine (K), and valine (V). Fmoc‐pentapeptides containing one E and one K all formed fibrillar nanostructures consisting of stacked β‐sheets. On the other hand, Fmoc‐pentapeptides containing two E and two K formed β‐sheet fibrils only when V was located at the center and separated two EK pairs. Photoluminescence studies of these peptides in a glycine buffer containing thioflavin T revealed a clear relationship between the amino acid sequence and secondary structure, where the location of neutral V plays a pivotal role for the β‐sheet formation. The β‐sheet formation propensity was further supported by computer simulation studies with the TANGO algorithm.