Some proteins are amyloidogenic, aggregating into toxic species. We design proteins with the aim of limiting that aggregation, slowing disease progression. With this goal in mind, we take advantage of the α-sheet secondary structure we observed in many amyloidogenic proteins. By designing peptides (short sequences of amino acids) with α-sheet structure, we found that these peptides preferentially interacted with the toxic intermediates in amyloidogenesis, inhibiting aggregation.
TEM imaging of biofilms with vehicle only and no peptide (A), 100 μM AP90 in 1.5% DMSO in carbonate buffer (B), and 50 μM AP193 dimer in 1.5% DMSO in carbonate buffer. Addition of α-sheet peptides led to almost no fibrillar material being visible outside of cells, compared to significant fibrillar material outside of cells without peptide added. (image source)