The simplest and minimal modification of a single amino acid or peptide bonds is
represented by N-methylation. This can improve the pharmacokinetic properties of biologically active
peptides as well as resulting in analogues that show specific biological activity such as enzyme
inhibitors, receptor antagonists and agonists, building blocks in combinatorial chemistry for the
screening of new potential drugs. Further, structural and conformational studies performed with
N-methylated analogues of natural amino acids and peptides enabled to (i) produce stable foldamers
with different topology with respect to the helix of natural and endogenous peptides, (ii) confer to
modified peptides high stability against proteases and (iii) enhance lipophilicity and bioavailability for pharmacological
purposes. Consequentially, it is crucial to provide optically pure N-methyl-amino acids and N-methylated peptides with a
large supply. The present report will focus on the results obtained in the last decade in the field of chemical synthetic
methodologies for the N-methylation of amino acids.
Keywords: N-methyl amino acids, N-methyl peptides, N-methylation, peptidomimetics.
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