Brief
Description:
The
technology presents a general method to generate cyclic peptides from
recombinant genetically encoded polypeptide precursors.
Applications:
This
methodology can be employed for the discovery and development of small molecules
with tailored binding affinity for therapeutic or biotechnological applications.
Specifically, this method can be applied for generating very large libraries of
structurally
diverse
cyclic peptides. Such libraries can be easily screened and deconvoluted to
identify ligands that can be used as capturing agents for biomolecules (e.g.
proteins, nucleic acids) in applications, such as affinity purification of
biomolecules from complex mixtures, in vivo and in vitro labeling of
biomolecules via affinity ligands, and protein capturing for proteomic analysis.
In addition, it can be applied to discover small molecule modulators of
biomolecular interactions (e.g. protein-protein, protein-nucleic acid, and
nucleic acid-nucleic acid interactions).
Advantages:
In
many cases, conformationally constrained peptides and peptide-containing
molecules exhibit enhanced proteolytic stability, favorable membrane-crossing
properties, and high affinity and selectivity in binding to a target
biomolecule. Owing to their high degree of structural and functional
complexity, peptide-based macrocycles
are also well suited for targeting extended biomolecular interfaces such as
those mediating protein-protein, protein-nucleic acid, and nucleic acid-nucleic
acid interactions. This invention presents a method for generating large
combinatorial libraries of peptide macrocycles constrained by non-reducible
thioether linkages. These libraries can be generated inside a living cell or as
part of a display platform such as phage display. These features make this
technology useful for enabling the discovery of bioactive cyclic peptides as
probe molecules or lead structures for further development into
drugs.