50 research outputs found
Design of Metastable β‑Sheet Oligomers from Natively Unstructured Peptide
Amyloid
oligomers represent the primary pathological species for neurodegenerative
diseases such as Alzheimer’s and Parkinson’s diseases.
Toxic oligomers are formed by many different proteins and peptides,
but their polydispersity makes them highly dynamic and heterogeneous.
One way to stabilize these structures is to prepare constrained peptides
that can be used to study amyloid intermediates, to identify oligomer-specific
drugs, and to generate conformational antibodies. These conformational
antibodies have demonstrated that oligomers share a common epitope.
In this research, we used a 40-amino acid unstructured segment of
prion protein (Prp) 109–148 with substitutions of methionine
for glycine (Prp-G) residues to prepare a stable and homogeneous population
of β-sheet oligomer mimics. These structures were characterized
by multiple biophysical and biochemical techniques that show characteristic
features of oligomers. Finally, this preparation was not detected
by three different sequence dependent prion antibodies