Peptide Macrocyclization Inspired by Non-Ribosomal Imine Natural Products.

ABSTRACT: A thermodynamic approach to peptide macrocyclization inspired by the cyclization of non-ribosomal peptide aldehydes is presented. The method provides access to structurally diverse macrocycles by exploiting the reactivity of transient macrocyclic peptide imines toward inter- and intramolecular nucleophiles. Reactions are performed in aqueous media, in the absence of side chain protecting groups, and are tolerant of all proteinogenic functional groups. Macrocyclic products bearing non-native and rigidifying structural motifs, isotopic labels, and a variety of bioorthogonal handles are prepared, along with analogues of four distinct natural products. Structural interrogation of the linear and macrocyclic peptides using variable-temperature NMR and circular dichroism suggests that preorganiza

SUBMITTER: Malins LR 

PROVIDER: S-EPMC5391502 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature