N-methylation of peptides on selected positions during the elongation of the peptide chain in solution phase.
[reactions: see text] An efficient and general solution-phase method for the site-specific N-methylation of peptides has been developed. This novel procedure involves synthesis of N-nosyl protected peptides and their subsequent N-methylation with diazomethane. Its efficiency was proved by the successful synthesis of various hindered oligopeptides containing N-methyl amino acid residues with excellent yield and purity. The method is particularly attractive in that the adopted conditions do not cause any detectable racemization of the peptide stereocenters and the process does not require chromatographic purification of the methylated products. A further advantage is the compatibility of this methodology with Fmoc solution-phase peptide synthesis.
Di Gioia
M Luisa
ML
Dipartimento di Scienze Farmaceutiche, Università della Calabria, Via Ponte P. Bucci cubo 15/C, I-87036 Arcavacata di Rende (CS), Italy.
Leggio
Antonella
A
Liguori
Angelo
A
D003978:Diazomethane / Q000737:chemistry; D008745:Methylation; D046908:Peptide Biosynthesis, Nucleic Acid-Independent; D010455:Peptides / Q000737:chemistry*; D012996:Solutions / Q000737:chemistry
D010455:Peptides; D012996:Solutions; D003978:Diazomethane