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.