A new amino acid, hybrid peptides and BODIPY analogs: synthesis and evaluation of 2-aminotroponyl-L-alanine (ATA) derivatives.

Abstract

Natural aromatic α-amino acid residues play critical roles in the structural and functional organization of proteins owing to π-interactions. Their aromatic residues are derived from benzenoid scaffolds. Non-benzenoid aromatic scaffolds such as tropone and tropolone are also constituents of troponoid natural products. Tropolone has also the ability to exhibit π-interactions along with additional hydrogen bonding. Thus, amino acids comprising troponyl could be potential building blocks of novel peptidomimetics. This report describes the synthesis of the L-aminotroponylalanine amino acid (ATA) and its unusual activity with the peptide coupling agent EDC. Importantly, its di-peptides form β-sheet/-turn type secondary structures in organic solvents owing to the troponyl residue. This amino acid is an excellent scaffold for the synthesis of fluorescent amino acids such as BODIPY amino acid analogs. Nevertheless, this amino acid and its BODIPY derivatives can enter HeLa cells without exhibiting significant cytotoxicity at low concentrations (∼50 μM). Hence, ATA and its BODIPY derivatives are promising aromatic amino acids for the construction of potential peptidomimetics and fluorescent labelling of target peptides.