Self‐assembly of a peptide with a tandem repeat of the Aβ16‐22 sequence linked by a β turn‐promoting dipeptide sequence. Issue 6 (November 2015)

• Record Type: Journal Article
• Authors: Sivakama Sundari, Chandrasekaran; Bikshapathy, Erugurala; Nagaraj, Ramakrishnan
• Is Part Of: Biopolymers. Volume 104:Issue 6(2015)
• Page Start: 790
• Page End: 803
• Publication Date: 2015-11
• Subjects: amyloid‐fibrils -- aromatic interactions -- beta hairpin -- fluorinated alcohols -- peptide self‐assembly; Biopolymers -- Periodicals; Peptides -- Periodicals; Spectrum analysis -- Periodicals; 572.33
• DOI: 10.1002/bip.22753
• Languages: English
• ISSNs: 0006-3525

Abstract

ABSTRACT: Amyloid deposits have been found to be abundant in patients with Alzheimer's disease due to fibril formation by the Aβ peptides. Peptide Aβ16‐22, comprising of the seven‐residue segment KLVFFAE, spanning residues 16–22 of the full length Aβ42 peptide, aggregates to form fibrils or other nanostructures in isolation, depending on the conditions of dissolution and incubation. In this study, we have examined the self‐assembly of PAβ, a tandem repeat peptide of the Aβ16‐22 sequence, joined by a β‐turn‐inducing sequence Asn‐Gly. To study the effect of various solvents on the self‐association, hexafluoroisopropanol (HFIP), trifluoroethanol (TFE) and methanol were used. The peptide was also incubated in fibril‐promoting conditions of 20% fluorinated alcohol–water mixtures which form dynamical solvent clusters, as well as in 20% MeOH–water mixture which does not form solvent clusters. Secondary structural studies suggest the presence of β‐structures. Electron microscopic images indicate that fibril formation occurs in a time‐dependent manner, under different conditions of solvent composition. Thioflavin‐T fluorescence studies confirm the presence of amyloid fibrils in the aggregates. Although the insertion of the Asn‐Gly sequence has not facilitated the formation of an ideal Type I' rigid turn, the intramolecular interactions aid the formation of a flexible β‐turn conformation, with twisted β‐sheets. Interactions between the intermolecular β‐sheets result in the formation of amyloid fibrils. Organic solvents appear to play an important role in modulating self‐assembly of peptide PAβ during fibril formation. Studies on β‐hairpin engineered amyloidogenic peptides could lead to knowledge about suitable conditions for generating a diverse range of polymorphic structures. © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 104: 790–803, 2015.