Conformational Analysis of Aβ-(25–35) Peptide by NMR: Insights into Secondary Structure and Aggregation Propensity

Abstract

In Alzheimer's disease, amyloid β (Aβ) is a principal component that accumulates within neuritic plaques. This disease is characterized by the aggregation of the protein Aβ (amyloid β) in the brain. Sequence GSNKGAIIGLM (Abeta 25-35) is the shortest toxic fragment of the protein Aβ-peptide, able to reproduce the aggregation process. NMR spectroscopy was utilized to investigate the spatial arrangement of the β-amyloid (25–35) peptide, which had been solubilized in water and HFIP at 25°C and prepared with an 80:20 D₂O/H₂O solvent mixture (900 µL). The XPLOR-NIH software (version 2.27) was used for the calculation and refinement of the three-dimensional structures. Using MOLMOL, the lowest-energy ten structural models were depicted and evaluated. NMR analysis of the Aβ-(25–35) peptide dissolved in the 20/80 HFIP and water mixture revealed that the C-terminal area tends to form more organized conformations, in contrast to the predominantly disordered nature of the N-terminal region observed in the structural overlays. Such conformational properties are anticipated to facilitate the design of molecules that can associate with amyloid peptides and act as inhibitors of their aggregation into fibrils.