Template-constrained macrocyclic peptides prepared from native, unprotected precursors

• DOI: 10.1073/pnas.1311706110
• Publication Date: 2013-09-17T04:23:51Z
• Authors: Kenneth V. Lawson; Tristan E. Rose; Patrick G. Harran
• Keywords: Chemoselectivity; Peptidomimetic; Scope (computer science); Ring size

Significance Cyclic peptides and peptidomimetics are valuable tools in biomedical research. This paper describes chemistry to convert linear, unmodified directly into stable, templated macrocycles. The ring-closing reaction is an allylic substitution catalyzed by palladium(0). It requires no tailored amino acid residues or protecting groups. proceeds rapidly at room temperature largely independent of product-ring size composition. catalysis shows broad scope predictable chemoselectivity while engaging functional groups native peptides. These methods could be applied broadly have special utility for those attempting perturb biological systems with unique small molecules.