Selective and potent proteomimetic inhibitors of intracellular protein-protein interactions

Anna Barnard, Kérya Long, Heather L Martin, Jennifer A Miles, Thomas A Edwards, Darren C Tomlinson, Andrew Macdonald, Andrew J Wilson
Angewandte Chemie 2015 March 2, 54 (10): 2960-5
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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