title: Solid-phase synthesis of NMe-IB-01212, a highly N-methylated cyclic peptide.
abstract: N-Methylation of peptides is an important synthetic tool in peptide-based medicinal chemistry. Herein, an optimized strategy for solid-phase synthesis of small but highly N-methylated cyclic peptides is described. The proposed route addresses several problems associated with the synthesis of peptides containing several sequential N-methyl-amino acids, such as in situ N-methylation, difficulty of acylation, epimerization, diketopiperazine formation, and stability at the NMe sites under trifluoroacetic acid exposure. The resulting NMe-IB-01212 exhibits micromolar activity and considerable stability.
authors.affiliation: Institute for Research in Biomedicine, Barcelona Science Park, Baldiri Reixac 10, 08028 Barcelona, Spain.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Marcucci
authors.forename: Judit
authors.initials: J
authors.lastname: Tulla-Puche
authors.forename: Fernando
authors.initials: F
authors.lastname: Albericio
mesh_terms: D003500:Cyclization; D047630:Depsipeptides / Q000138:chemical synthesis*; D007536:Isomerism; D008745:Methylation; D015394:Molecular Structure; D060327:Solid-Phase Synthesis Techniques
chemical_list: D047630:Depsipeptides; C519452:IB-01212