Peptide macrocycles featuring a backbone secondary amine: a convenient strategy for the synthesis of lipidated cyclic and bicyclic peptides on solid support.
A convenient strategy for the on-resin synthesis of macrocyclic peptides (3- to 13-mers) via intramolecular halide substitution by a diamino acid is described. The method is compatible with standard Fmoc/tBu SPPS and affords a tail-to-side-chain macrocyclic peptide featuring an endocyclic secondary amine. This functional group is still reactive toward acylation, allowing for the continuation of the synthesis. An application to the synthesis of lipidated cyclic and bicyclic antimicrobial peptides is presented.
Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark.
Alberto
A
Oddo
Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark.
Lena
L
Münzker
Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark.
Paul R
PR
Hansen
D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D023181:Antimicrobial Cationic Peptides; D010455:Peptides; D010456:Peptides, Cyclic