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.