Conformational Analysis of the β-amyloid Peptide Fragment, β(12–28)

Abstract

NMR and CD spectroscopy have been used to examine the conformation of the peptide, beta(12-28), (VHHQKLVFFAEDVGSNK) in aqueous and 60% TFE / 40% H2O solution at pH 2.4. In 60% TFE solution, the peptide is helical as confirmed by the CD spectrum and by the pattern of the NOE cross peaks detected in the NOESY spectrum of the peptide. In aqueous solution, the peptide adopts a more extended and flexible conformation. Broadening of resonances at low temperature, temperature-dependent changes in the chemical shifts of several of the CH alpha resonances and the observation of a number of NOE contacts between the hydrophobic side-chain protons of the peptide are indicative of aggregation in aqueous solution. The behavior of beta(12-28) in 60% TFE and in aqueous solution are consistent with the overall conformation and aggregation behavior reported for the larger peptide fragment, beta(1-28) and the parent beta-amyloid peptide.

The Arctic mutation alters helix length and type in the 11–28 β-amyloid peptide monomer—CD, NMR and MD studies in an SDS micelle

“…(Rodziewicz-Motowidło et al, 2007)). These studies led to the conclusion that Ab peptides form mainly a-heli- Ab(12-28) peptide forms an a-helical structure involving residues 16-24 in aqueous solutions of SDS or TFE (Jayawickrama et al, 1995;Fletcher and Keire, 1997). The structures of the peptide obtained in this work are mostly a-helical in the region 16-24 and are very similar to the structures of the Ab(12-28) peptide fragment proposed by Fletcher and Keire.…”

Structural insights for designed alanine‐rich helices: Comparing NMR helicity measures and conformational ensembles from molecular dynamics simulation

“…The recent investigations of amyloid fibrils have also found that sequences that adopt α-helices in globular proteins can form β–strands in amyloid aggregates 8, 9 . The quest to understand these secondary structure transitions has, once again, brought helix studies into the spotlight.…”

Risk factors for hypopharyngeal/upper esophageal stricture formation after concurrent chemoradiation

“…The syrian hamster Prion protein residues 109–122 (H1 peptide) is considered to be important for the α‐to‐β conformational transition that leads to amyloid formation, and is responsible for prion diseases. According to several experimental evidences on the isolated H1 peptide, it adopts very rapidly in water β‐sheet structure from which amyloid fibrils precipitate,17, 18 while in 2,2,2‐trifluoroethanol (TFE) or membrane‐mimicking environments the H1 peptide adopts an α‐helical conformation 19, 20. These properties make the study of this peptide very interesting, and may provide a key for understanding protein folding or the cause of amyloid diseases.…”