Novel synthetic agents designed to target protein-protein interactions (PPIs) and protein-membrane interactions (PMIs) provide an alternative therapeutic approach where traditional drug discovery methods have been unsuccessful. Small-molecule organic compounds that recapitulate the features of short peptides (peptidomimetics) and larger protein surfaces (proteomimetics) may be used as tools to guide drug discovery or as drug candidates themselves.<br/>The research presented here involves the design, synthesis, and characterization of peptidomimetic and proteomimetic compounds that target PPIs and PMIs by folding into predicted structures and displaying functional groups with a chemical density and diversity that rivals their biological counterparts. Hydrogen bond organized derivatives of the dipeptide mimetic <i>meta</i>-aminomethylbenzoic acid (MAMBA) were synthesized in multi-gram quantities with facile purification techniques and good yield from the commodity chemical beta-resorcylic acid. The MAMBA monomers were amenable to solution and solid phase coupling methodologies.<br/>MAMBA oligomers were characterized by NMR spectroscopy, mass spectrometry, and X-ray diffraction techniques. The MAMBA scaffold was shown to have the predicted hydrogen bonding pattern in solution and solid phases and was shown to template beta-strand formation in peptides. The MAMBA scaffold is synthetically accessible and easily functionalized, thus demonstrating its potential to mimic diverse and chemically complex protein epitopes. The development of biomimetic synthetic regulators of complex protein interactions is of great clinical interest and provides new opportunities to study and rectify human disease states.

MAMBA: Hydrogen bond organized beta-strand peptidomimetics

254th National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.