Aza-β^<i>3</i>-cyclotetrapeptides

The cyclization of aza-β3-tetrapeptides gives access to new CTP (cyclotetrapeptide) analogues. These stereocontrolled templates are assembled without any asymmetric synthesis. X-ray crystallographic structure and NMR analysis show that the macrocyclic scaffold is characterized by a fully cooperative intramolecular H-bond network, in sharp contrast with the nanotubular assemblies observed for β3-cyclotetrapeptides. This folding property reduces considerably the polarity of aza-β3-tetrapeptides and should be useful in addressing intracellular targets.