Synthesis of N-methylated cyclic peptides

Jayanta Chatterjee, Burkhardt Laufer, Horst Kessler

Research output: Contribution to journalArticlepeer-review

107 Scopus citations

Abstract

This protocol presents a detailed description of the synthesis of N-methylated cyclic peptides. N-methylation is a powerful technique to modulate the physicochemical properties of peptides by introducing one or more methyl groups into the peptidic amide bonds. Together with peptide cyclization, this procedure confers unprecedented pharmacokinetic properties to the peptides, including metabolic stability, membrane permeability and even oral bioavailability. Here we describe two simplified methods of N-methylation of linear peptides on solid supports, which can be performed in less than 2 h and are applicable to any amino acid. Finally, we also describe two methods of peptide cyclization, which can be used to obtain the N-methylated cyclic peptide and which are not limited to specific peptide sequences. With this protocol, multiply N-methylated cyclic peptides can be synthesized in as little as 4-5 d.

Original languageEnglish
Pages (from-to)432-444
Number of pages13
JournalNature Protocols
Volume7
Issue number3
DOIs
StatePublished - Mar 2012

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