Helix Stabilized, Thermostable, and Protease-Resistant
Self-Assembled Peptide Nanostructures as Potential Inhibitors of Protein–Protein
Interactions
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Abstract
Self-assembled peptide nanostructures
with actively folded secondary
structures have potential to mimic the function of proteins. We here
show that α-helix-stabilized self-assembled peptide nanostructures
(αSSPNs), whose sizes are comparable to those of proteins, have
potential to be developed as protein–protein interaction (PPI)
inhibitors along with several unprecedented properties. Using p53-MDM2
PPI as a model system, the molecular recognition and modulation of
PPIs by αSSPN grafted with a p53 α-helix (p53 αSSPN)
were investigated. The competition assay showed that the p53 αSSPN
can inhibit the p53-MDM2 interaction. Interestingly, the p53 αSSPN
was far more resistant to degradation by the protease chymotrypsin
than the monomeric p53 peptide and had high thermal stability. These
results suggest that the αSSPN scaffold holds great potential
to be developed as a novel class of PPI inhibitors