Towards more drug-like proteomimetics: two-faced, synthetic α-helix mimetics based on a purine scaffold.
نویسندگان
چکیده
Mimicry of two faces of an α-helix might yield more potent and more selective inhibitors of aberrant, helix-mediated protein-protein interactions (PPI). Herein, we demonstrate that a 2,6,9-tri-substituted purine is capable of disrupting the Mcl-1-Bak-BH3 PPI through effective mimicry of key residues on opposing faces of the Bak-BH3 α-helix.
منابع مشابه
Selective and Potent Proteomimetic Inhibitors of Intracellular Protein–Protein Interactions†
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...
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ورودعنوان ژورنال:
- Organic & biomolecular chemistry
دوره 13 32 شماره
صفحات -
تاریخ انتشار 2015