Conformational analysis of amyloid precursor protein fragment containing amino acids 667–676, and the effect of d-Asp and iso-Asp substitution at Asp672 residue

Amyloid precursor protein (APP) fragment containing amino acids 667–676, (APP667–676), is a substrate for β-secretase which is responsible for generating amyloid β peptides. Conformational analysis of APP667–676 peptide [Ac-Ser-Glu-Val-Lys-Met-Asp-Ala-Glu-Phe-Arg-NH2] and the effect of substitution of Asp672 with d-Asp and iso-l-Asp, studied for the first time, demonstrate that the peptide backbone of APP667–676 is flexible and adopts different conformations in different solvent environments (water, trifluoroethanol and dimethylsulfoxide). A major conformational difference was observed in trifluoroethanol solvent when Asp672 is substituted with d-Asp and iso-Asp. These conformational changes involved in APP667–676 may assist in understanding the interactions between β-secretase and APP667–676, with relevance to Alzheimer’s disease.