Fai Alotaibi, Meisel Lab Graduate Student, GW Department of Chemistry

Protein-protein interactions (PPIs) are essential for many biological processes. Aberrant PPIs are also the molecular basis of many diseases, making them an attractive target for therapeutic intervention. Peptidomimetics, which are synthetic compounds that mimic the structures and functions of peptides, can be designed to modulate PPIs. Foldamers are synthetic oligomers with well-defined secondary and tertiary structures. Foldamers can be designed as peptidomimetics, making them promising scaffolds for targeting PPIs.

In this project, a series of arylamide foldamers were developed aiming to improve the conformation control using hydrogen bonding, stereosequence, and a bridging group. Nuclear magnetic resonance and circular dichroism spectroscopy were used to compare the conformations of this foldamer series in solution. We determined that using the bridging group and stereosequence in addition to hydrogen bonding significantly improved their folding compared to using hydrogen bonding alone. Furthermore, we developed a robust structure-based computational workflow to identify potential peptidomimetic compounds from a virtual foldamer library using a model of the PPI complex and commercially available software.