Selective and Potent Proteomimetic Inhibitors of Intracellular Protein-Protein Interactions
Anna Barnard1, Kérya Long1, Heather L Martin2
1School of Chemistry, University of Leeds, Woodhouse Lane, Leeds LS2 9JT (UK); Astbury Centre For Structural Molecular Biology, University of Leeds, Woodhouse Lane, Leeds LS2 9JT (UK).
Abstract:
Inhibition of protein-protein interactions (PPIs) represents a major challenge in chemical biology and drug discovery. α-Helix mediated PPIs may be amenable to modulation using generic chemotypes, termed "proteomimetics", which can be assembled in a modular manner to reproduce the vectoral presentation of key side chains found on a helical motif from one partner within the PPI. In this work, it is demonstrated that by using a library of N-alkylated aromatic oligoamide helix mimetics, potent helix mimetics which reproduce their biophysical binding selectivity in a cellular context can be identified.
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