Amyloidogenic Peptide/Single-Walled Carbon Nanotube Composites Based on Tau-Protein-Related Peptides Derived from AcPHF6: Preparation and Dispersive Properties

We investigated the abilities of a family of tau-protein-related amphiphilic peptides with predictable self-association characteristics (<i>N</i>-acetyl-VQIVXK-NH₂ (X = F, L, V, W, Y, A, K)) to disperse single-walled carbon nanotubes (SWCNTs). The dispersion abilities of these peptides could be explained by a linear combination of their hydrophobic and amyloidogenic properties in a 60/40 ratio. Circular dichroism (CD) spectra of one of the peptides having a high propensity to form an amyloid (<i>N</i>-acetyl-VQIVYK-NH₂ (AcPHF6)) showed that this peptide exists as a random coil in water but assumes a β-sheet conformation when sonicated with SWCNTs. Electron microscopy results, changes in near-infrared spectra, and changes in the Raman spectra upon formation of composites suggest that AcPHF6 intercalates, coats, and exfoliates SWCNT bundles. N-terminal truncation of AcPHF6 greatly reduced its ability to disperse SWCNTs. Taken together, our results suggest that amyloidogenic peptides wrap SWCNTs, forming an extensive β-sheet network. To date, peptides based on the AcVQIVXK framework are structurally the simplest peptides that have been found to disperse CNTs, and an understanding of those properties that determine their efficiency may be used to design even more efficient peptides for these purposes. We believe that due to the structural simplicity, this family of peptides will have clear synthetic advantages over peptides now known to disperse CNTs

Macrocyclic β-Sheet Peptides That Inhibit the Aggregation of a Tau-Protein-Derived Hexapeptide

This paper describes studies of a series of macrocyclic β-sheet peptides <b>1</b> that inhibit the aggregation of a tau-protein-derived peptide. The macrocyclic β-sheet peptides comprise a pentapeptide “upper” strand, two δ-linked ornithine turn units, and a “lower” strand comprising two additional residues and the β-sheet peptidomimetic template “Hao”. The tau-derived peptide Ac-VQIVYK-NH₂ (AcPHF6) aggregates in solution through β-sheet interactions to form straight and twisted filaments similar to those formed by tau protein in Alzheimer’s neurofibrillary tangles. Macrocycles <b>1</b> containing the pentapeptide VQIVY in the “upper” strand delay and suppress the onset of aggregation of the AcPHF6 peptide. Inhibition is particularly pronounced in macrocycles <b>1a</b>, <b>1d</b>, and <b>1f</b>, in which the two residues in the “lower” strand provide a pattern of hydrophobicity and hydrophilicity that matches that of the pentapeptide “upper” strand. Inhibition varies strongly with the concentration of these macrocycles, suggesting that it is cooperative. Macrocycle <b>1b</b> containing the pentapeptide QIVYK shows little inhibition, suggesting the possibility of a preferred direction of growth of AcPHF6 β-sheets. On the basis of these studies, a model is proposed in which the AcPHF6 amyloid grows as a layered pair of β-sheets and in which growth is blocked by a pair of macrocycles that cap the growing paired hydrogen-bonding edges. This model provides a provocative and appealing target for future inhibitor design