Aza-peptides: expectations and reality

Abstract

The replacement of the α-carbon atom in an α-amino acid structure by a nitrogen atom yields alkylcarbazic acids, also known as α-aza amino acids. Although the topology of α-amino acids and α-aza amino acids is similar, their chemical and stereochemical properties are significantly different. For this reason, the application of the common solid-phase peptide synthesis (SPPS) protocol cannot be used for aza-peptide bond synthesis without changes. On the other hand, the aza-peptide bond is more stable than the common peptide bond, therefore these compounds are very attractive targets for drug design. In this review, we summarize data on aza-peptide bond chemistry, with implications for the improvement of aza-peptide chemical synthesis.

Keywords

• aza-amino acid precursors
• aza-peptide synthesis
• aza-amino acid chemistry
• hydrazine derivatives
• activators
• limits of spps protocol for aza-peptide synthesis.