Beta-amino acids are analogs of alpha-amino acids where the amino group is attached to the beta-carbon instead of the alpha-carbon. The most common and well known beta-amino acid is beta-alanine, as known as 3-aminopropionic acid. Other beta amino acids that are found in natural products are beta-phenylalanine, beta-tyrosine, and their derivatives.
Peptides containing beta-amino acid residues tend to have increased resistance to enzymatic degradation. Peptides containing two beta-phenylalanines, for instance, have been reported to be resistant to carboxypeptidase and chymotripsin. Thus incorporating beta-amino acids can improve the half-life of potential peptide drugs.
Beta-phenylalanine and beta-tyrosine are components of many natural products with interesting biological activity. Alveolamides A, B and C are peptides isolated from Microascus alveolaris which contain beta-phenylalanine. These peptides have anti-fungal activity against phytopathogenic fungi. Beta-phenylalanine is also a component of astins A, B, and C, alkaloids isolated from the roots of Aster tataricus. Astin C, later shown to be produced by the fungal endophyte Cyanodernella asteris, specifically inhibits the innate immune CDN sensor STING. Misregulation of this sensor promotes cancer and autoimmune or autoinflammatory disorders.
Beta-tyrosine residues are a part of the depsipeptides named jaspamides. Isolated from the marine sponce Jaspis, jaspamides have potent insecticidal activity against Heliothis virescens and antimicrobial activity against Candida albicans.
The D and L nomeclature has not been applied consistently to beta-amino acids. To avoid confusion, AAPPTec uses R and S nomeclature with beta-amino acids.