Aggregation of amyloid beeta 1-42 (Aβ<sub>42</sub>)
peptide causes the formation of clustered deposits knows as amyloid plaques in
the brain which leads to neuronal dysfunction and memory loss and associated with
many neurological disorders including Alzheimer’s and Parkinson’s. Aβ<sub>42</sub>
has core structural motif with phenylalanine at the 19 and 20 positions. The
diphenylalanine (FF) residue plays a crucial role in the formation of amyloid fibers
and serves as model peptide for studying Aβ<sub>42 </sub>aggregation. FF
self-assembles to well-ordered tubular morphology via aromatic pi-pi stackings.
Our studies, suggest that the aromatic rings present in the anti-amyloidogenic compounds
may interact with the pi-pi stacking interactions present in the FF. Even the
compounds which do not have aromatic rings, like cyclodextrin and cucurbituril
show anti-amyloid property due to the binding of aromatic ring inside the guest
cavity. Hence, our studies also suggest that compounds which may have a
functional moiety capable of interacting with the aromatic stacking interactions
might be tested for their anti-amyloidogenic properties. Further, in this
manuscript, we have proposed two novel nanoparticle based assays for the rapid
screening of amyloid inhibitors. In the first assay, interaction between biotin-tagged
FF peptide and the streptavidin labelled gold nanoparticles (s-AuNPs) were
used. In another assay, thiol-Au interactions were used to develop an assay for
detection of amyloid inhibitors. It is envisaged that the proposed analytical method
will provide a simple, facile and cost effective technique for the screening of
amyloid inhibitors and may be of immense practical implications to find the therapeutic
remedies for the diseases associated with the protein aggregation.
Importance of the Cyclic Cystine Knot Structural Motif for Immunosuppressive Effects of Cyclotides
