Document Type
Article
Publication Date
4-6-2009
Abstract
The use of peptides as drugs in pharmaceutical applications is hindered by their susceptibility to proteolysis and therefore low bioavailability. β‐Peptides that contain an additional methylene group in the backbone, are gaining recognition from a pharmaceutical stand point as they are considerably more resilient to proteolysis and metabolism. Recently, we reported two new classes of β‐peptides, β3‐ and β2‐peptides derived from l‐aspartic acid and l‐diaminopropionic acid, respectively. Here, we report the proteolytic stability of these β‐peptidic compounds and a mixed α /β‐peptide against three enzymes (pronase, trypsin and elastase), as well as, human serum. The stability of these peptides was compared to an α‐peptide. Peptides containing β‐linkages were resistant to all conditions. The mixed α /β‐peptide, however, exhibited proteolysis in the presence of trypsin and pronase but not elastase. The rate of degradation of the mixed α /β‐peptide was slower than that would be expected for an α‐peptide. In addition, these β‐peptides were not toxic to HeLa and COS‐1 cell lines as observed by MTT cytotoxicity assay. These results expand the scope of mixed α /β‐peptides containing β‐amino acids or small β‐peptide fragments as therapeutic peptides.
Recommended Citation
Ahmed S, Kaur K. The proteolytic stability and cytotoxicity studies of l-aspartic acid and l-diaminopropionic acid derived β-peptides and a mixed α/β-peptide. Chem. Biol. Drug Des. 2009;73(5):545-552. doi: 10.1111/j.1747-0285.2009.00803.x
Copyright
Wiley
Included in
Amino Acids, Peptides, and Proteins Commons, Medical Biochemistry Commons, Medicinal and Pharmaceutical Chemistry Commons, Other Pharmacy and Pharmaceutical Sciences Commons
Comments
This is the accepted version of the following article:
Ahmed S, Kaur K. The proteolytic stability and cytotoxicity studies of l-aspartic acid and l-diaminopropionic acid derived β-peptides and a mixed α/β-peptide. Chem. Biol. Drug Des. 2009;73(5):545-552.
which has been published in final form at DOI: 10.1111/j.1747-0285.2009.00803.x. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.