Schellman motif in dehydrooligopeptides: crystal and molecular structure of Boc-Val-ΔPhe-Leu-Phe-Ala-ΔPhe-Leu-OMe

Secondary structural motifs found in peptides are also generated in model compounds containing α, β-didehydrophenylalanine residues (ΔPhe). A short peptide containing two ΔPhe units, Boc-Val-ΔPhe-Leu-Phe-Ala-ΔPhe-Leu-OMe, was found to assume a 3<SUB>10</SUB>/α-helical conformation terminated by a Schellman motif

Aβ1─42 C-terminus fragment derived peptides prevent the self-assembly of the parent peptide

A series of peptides derived from the C-terminus fragment (Aβ38–42) of Aβ showed significant to complete reduction in Aβ-induced toxicity

C‑Terminal Fragment, Aβ_32–37, Analogues Protect Against Aβ Aggregation-Induced Toxicity

Amyloid-β aggregation is a major etiological phenomenon in Alzheimer’s disease. Herein, we report peptide-based inhibitors that diminish the amyloid load by obviating Aβ aggregation. Taking the hexapeptide fragment, Aβ_32–37, as lead, more than 40 new peptides were synthesized. Upon evaluation of the newly synthesized hexapeptides as inhibitors of Aβ toxicity by the MTT-based cell viability assay, a number of peptides exhibited significant Aβ aggregation inhibitory activity at sub-micromolar concentration range. A hexapeptide (<b>1</b>) showed complete mitigation of Aβ toxicity in the cell culture assay at 2 μM. In the ThT fluorescence assay, upon incubation of Aβ with this peptide, we observed no increase in the ThT fluorescence relative to control. The secondary structure estimation by circular dichroism spectroscopy and morphological examination by transmission electron microscopy further confirmed the results