The proteolytic stability and cytotoxicity studies of L-aspartic acid and L-diaminopropionic acid derived beta-peptides and a mixed alpha/beta-peptide.

The use of peptides as drugs in pharmaceutical applications is hindered by their susceptibility to proteolysis and therefore low bioavailability. beta-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 beta-peptides, beta(3)- and beta(2)-peptides derived from L-aspartic acid and L-diaminopropionic acid, respectively. Here, we report the proteolytic stability of these beta-peptidic compounds and a mixed alpha /beta-peptide against three enzymes (pronase, trypsin and elastase), as well as, human serum. The stability of these peptides was compared to an alpha-peptide. Peptides containing beta-linkages were resistant to all conditions. The mixed alpha /beta-peptide, however, exhibited proteolysis in the presence of trypsin and pronase but not elastase. The rate of degradation of the mixed alpha /beta-peptide was slower than that would be expected for an alpha-peptide. In addition, these beta-peptides were not toxic to HeLa and COS-1 cell lines as observed by MTT cytotoxicity assay. These results expand the scope of mixed alpha /beta-peptides containing beta-amino acids or small beta-peptide fragments as therapeutic peptides.