Modular Assembly of Macrocyclic Organo-Peptide Hybrids Using Synthetic and Genetically Encoded Precursors

摘要

Macrocyclic peptides and peptide-containing molecules are attractive molecular scaffolds for the development of bioac-tive compounds to modulate biomolecular interactions. These structures combine a high degree of functional complexity with restricted conformational flexibility, which make them well-suited to achieve selective and tight binding to extended biomolecular interfaces, such as those mediating protein-protein and protein-nucleic acid complex formation. Compared to linear peptides, conformationally constrained pep-tide-based ligands often exhibit higher proteolytic stability, enhanced cell permeability, and higher affinity towards the target biomolecule, which render them valuable as probes and potential pharmacological agents. Indeed, many cyclic and lariat peptides isolated from natural sources exhibit potent biological activities and have provided a source of viable drugs.