Peptides characterized by single or multiple N-methylated, C-alpha-trisubstituted (e.g., protein) amino acids are of great interest in medicinal chemistry. Several naturally occurring peptides, remarkably stable to enzymatic attacks, are based on N-methylated residues. The classical conditions (CH3I/Ag2O in DMF, 24 h, room temperature) for N-methylation of the peptide function are useful tools for distinguishing solvent exposed from intramolecularly H-bonded -CO-NH-groups in peptides. In this work we have extended this reaction to N-alpha-acylated, linear peptides based exclusively on helicogenic C-alpha-tetrasubstituted alpha-amino acids, e.g., Aib (alpha-aminoisobutyric acid) or (alpha Me)Nva (C-alpha-methyl norvaline) residues. Under the experimental conditions used, only amide monomethylation (on the N-terminal, acylated, residue) takes place.

N-Methylation of N alpha-Acetylated, Fully C alpha-Ethylated, Linear Peptides

MORETTO, ALESSANDRO;DE ZOTTI, MARTA;FORMAGGIO, FERNANDO;TONIOLO, CLAUDIO
2008

Abstract

Peptides characterized by single or multiple N-methylated, C-alpha-trisubstituted (e.g., protein) amino acids are of great interest in medicinal chemistry. Several naturally occurring peptides, remarkably stable to enzymatic attacks, are based on N-methylated residues. The classical conditions (CH3I/Ag2O in DMF, 24 h, room temperature) for N-methylation of the peptide function are useful tools for distinguishing solvent exposed from intramolecularly H-bonded -CO-NH-groups in peptides. In this work we have extended this reaction to N-alpha-acylated, linear peptides based exclusively on helicogenic C-alpha-tetrasubstituted alpha-amino acids, e.g., Aib (alpha-aminoisobutyric acid) or (alpha Me)Nva (C-alpha-methyl norvaline) residues. Under the experimental conditions used, only amide monomethylation (on the N-terminal, acylated, residue) takes place.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11577/2444982
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