Multicomponent diversity-oriented synthesis of aza-lysine-peptide mimics.

Copper catalyzed coupling of Mannich reagents to aza-propargylglycine residues has been employed to synthesize constrained aza-lysine peptides. Employing growth hormone releasing peptide-6 (GHRP-6) as a model peptide and a variety of secondary amines, 18 aza-Lys analogs were synthesized by this so-called A(3)-coupling reaction. This effective method for making constrained aza-Lys-peptides offers strong potential for exploring various recognition events implicating lysine residues including post-translational peptide modification.