The synthesized peptoid, JPT1, which had been previously found to inhibit amyloid-beta (Aβ) aggregation, has been shown to interact with several other proteins that have an anti-parallel beta-sheet structure. JPT1 was originally designed to mimic the peptide KLVFF, which interacts with Aβ’s hydrophobic core. However, we have found that a defined hydrophobic core is not required for JPT1 to display activity. JPT1 was shown to inhibit amylin aggregation effectively. Amylin is a 3.9 kDa amyloidgenic peptide which forms aggregates similar to Aβ, but with multiple amino acids along the entire length of the peptide mediating anti-parallel beta-sheet formation. Another class of beta-sheet proteins, such as Green Fluorescent Protein (GFP), forms multiple anti-parallel beta-sheets into a β- barrel structure. The presence of JPT1 was found to affect the degree to which the GFP maintains fluorescence over time increasing the stability. Finally, we have also studied JPT1’s ability to alter the solubility of Staphylococcal nuclease mutants, where mutations may have altered regions next to the beta-sheets crucial for native conformation. Furthermore, our data suggest that JPT1 can serve as both a stabilizing and destabilizing agent for anti-parallel beta-sheets in multiple proteins. JPT1 may represent a novel class of peptoid specific to beta-sheet interactions.

Characterization of a hydrophobic peptoid which interacts with beta-sheet proteins

249th National Meeting (2015)

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