Alpha-Helix Mimicry

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Brief Description:   The technology presents novel macrocyclic peptidomimetic molecules and a method to generate these molecules for targeting alpha-helix-mediated protein-protein and protein-nucleic acid interactions.   Applications:   This methodology can be employed for the development of low molecular-weight molecules for therapeutic or biotechnological applications. Specifically, the method of the invention is useful toward generating and identifying structurally and proteolytically stable peptidomimetics of alpha-helical functional motifs in proteins. The method can also be applied to discover small molecules that modulate protein-protein or protein-nucleic acid interactions mediated by alpha-helical recognition motifs.   Advantages:   A large fraction of protein-protein and protein-nucleic acid interactions are mediated by well defined alpha-helical motifs. Linear peptides spanning these regions are, however, unsuitable for in vivo applications and/or use as therapeutic agents due to poor proteolytic stability, low cell permeability, and promiscuity in binding due to conformational flexibility. This invention presents a method for generating peptidomimetics that reproduce the functional properties of alpha-helical recognition motifs while possessing increased structural stability, proteolytic resistance and cell permeability. This technology is thus useful toward enabling the discovery of bioactive compounds as probe molecules or lead structures for further development into drugs for a wide variety of target proteins and biomolecular interactions.