Study of the non-proteinogenic delta-amino acid ACCA, its biological investigation and application

Abstract

The aim of this project is the investigation of the novel non-proteinogenic δ-amino acid cis-3-(aminomethyl)cyclobutane carboxylic acid (ACCA) and its possible applications.ACCA was obtained after a 7 steps synthesis, from commercially available starting materials. The important characteristics of ACCA are the locked cis conformation of the amino and carboxylic acid groups and the presence of the cyclobutane moiety that render it a constrained molecule and therefore particularly interesting as building block for organic synthesis and peptidomimetics drug design. For these reasons ACCA can be considered a very versatile and useful molecule, with applications in different research fields, some of which are described herein.A small library of dipeptides was also synthesised coupling ACCA with proteinogenic amino acids.Considering ACCA resemblance with the neurotransmitter glutamic acid, the neural activity of the δ-amino acid, its ester and dipeptides have been investigated on rat C6 glioma cells through glutamate uptake experiments, showing an interesting increase in glutamate uptake.Herein the incorporation of ACCA in a macrocycle tetrapeptide mimic, with potential as ligand for metal ions is also reported.