*Email correspondence to: james.gardiner@csiro.au
β-Amino acids and their derivatives occur as natural building blocks of many natural products (eg bestatin, dolastatin, microcystin) as well as in commercially available pharmaceuticals (eg Taxol®, Januvia®). In 1996, β-peptides consisting of β-amino acids with proteinogenic side chains were synthesized and described for the first time.(1) Since then β-peptides have been found to adopt a wide variety of structural motifs, (helices, sheets and turns) similar to that of α-peptides, and have demonstrated remarkable stability to a wide variety of proteolytic and metabolizing enzymes. As a result β-peptides have been explored as proteolytically stable mimics of α-peptides for a range of therapeutic and biomedical applications. Examples include inhibitors of protein-protein interactions and viral cell entry, ligands for the somatostatin receptor and MHC complex, cell-penetrating peptides, and antifungal and antimicrobial agents.(2) While the extraordinary metabolic stability of β-peptides has been a great advantage in therapeutic development it has also led to some concern with regard to a general biodegradability of such compounds. As β-amino acids and β-peptides are applied in medicinal and materials chemistry, ecological considerations become important as such compounds eventually make their way into the environment.
In 2005 a novel bacterial strain capable of growing solely on short β-tripeptides was discovered.(3) The β-peptide-degrading enzyme (β-peptidase) was isolated and characterized, and shown to effectively degrade β-peptides with specific side chains. Shortly afterwards two other related enzymes, members of the N-terminal hydrolase superfamily, were also shown to effectively cleave β-peptides. A brief description of the discovery and properties of these enzymes will be given.
Furthermore, we present here for the first time the discovery of 4 further organisms capable of degrading β-peptides, including one example where the activity is 10,000 times that of previously reported examples. The organisms expressing β-peptidases are widely varied leading to speculation as to the natural role of these enzymes. A description will be given of the structure and properties of these newly discovered β-peptidases, their relationship to previously discovered examples, their use in peptide synthesis, and their application towards the formation of self-assembled soft materials for biomedical applications.