Template-constrained macrocyclic peptides prepared from native, unprotected precursors.

ABSTRACT: Peptide-protein interactions are important mediators of cellular-signaling events. Consensus binding motifs (also known as short linear motifs) within these contacts underpin molecular recognition, yet have poor pharmacological properties as discrete species. Here, we present methods to transform intact peptides into stable, templated macrocycles. Two simple steps install the template. The key reaction is a palladium-catalyzed macrocyclization. The catalysis has broad scope and efficiently forms large rings by engaging native peptide functionality including phenols, imidazoles, amines, and carboxylic acids without the necessity of protecting groups. The tunable reactivity of the template gives the process special utility. Defined changes in reaction conditions markedly alter chemoselectivi

SUBMITTER: Lawson KV 

PROVIDER: S-EPMC3791740 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature