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, (APP(667-676)), is a substrate for beta-secretase which is responsible for generating amyloid beta peptides. Conformational analysis of APP(667-676) peptide [Ac-Ser-Glu-Val-Lys-Met-Asp-Ala-Glu-Phe-Arg-NH2] and the effect of substitution of Asp(672) with D-Asp and iso-L-Asp, studied for the first time, demonstrate that the peptide backbone of APP(667-676) is flexible and adopts different conformations in different solvent environments (water, trifluoroethanol and dimethylsulfoxide). A major conformational difference was observed in trifluoroethanol solvent when Asp(672) is substituted with D-Asp and iso-Asp. These conformational changes involved in APP(667-676) may assist in understanding the interactions between beta-secretase and APP(667-676), with relevance to Alzheimer's disease. (C) 2012 Elsevier Inc. All rights reserved.