5-Amino-3-methyl-Isoxazole-4-carboxylic Acid as a Novel Unnatural Amino Acid in the Solid Phase Synthesis of α/β-Mixed Peptides

The hybrid peptides consisting of alpha and beta-amino acids show great promise as peptidomimetics that can be used as therapeutic agents. Therefore, the development of new unnatural amino acids and the methods of their incorporation into the peptide chain is an important task. Here, we described our investigation of the possibility of 5-amino-3-methyl-isoxazole-4-carboxylic acid (AMIA) application in the solid phase peptide synthesis. This new unnatural beta-amino acid, presenting various biological activities, was successfully coupled to a resin-bound peptide using different reaction conditions, including classical and ultrasonic agitated solid-phase synthesis. All the synthesized compounds were characterized by tandem mass spectrometry. The obtained results present the possibility of the application of this beta-amino acid in the synthesis of a new class of bioactive peptides.

Automated summary

Hybrid peptides composed of alpha and beta-amino acids have potential as therapeutic agents. Therefore, the development of new unnatural amino acids and methods for their incorporation is important. In this study, we investigated the application of 5-amino-3-methyl-isoxazole-4-carboxylic acid (AMIA) in solid phase peptide synthesis. The results show that this unnatural beta-amino acid can be used in synthesizing a new class of bioactive peptides.