The structure of well-folded beta-hairpin peptides promotes resistance to peptidase degradation.
To investigate the effect of peptide secondary structure on proteolytic resistance, we have synthesized a series of peptides based on a well-folded beta-hairpin, WKWK. Mutations were made within the peptide which either decreased or increased the propensity to form beta-hairpin structures and one scrambled sequence was used as an unstructured control. The peptides were incubated with three different enzymes, alpha-chymotrypsin, trypsin, and pronase E, which represented both specific and non-specific proteases. The reactions were quenched at varying time points and analyzed with RP-HPLC to determine the rate of degradation for each of the peptides. We found that an increase in structure correlates well with an increase in resistance to degradation. We have shown that having both strong side chain interactions and a rigid D-Pro-Gly beta-turn resulted in the most proteolytic resistant peptides. The results from this study suggest that beta-hairpin structure is a viable way to provide added protease resistance to a peptide.
Cline
Lauren L
LL
Department of Chemistry, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Waters
Marcey L
ML
D000818:Animals; D002417:Cattle; D002918:Chymotrypsin / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D011402:Pronase / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary
D010455:Peptides; D002918:Chymotrypsin; C117608:alpha-chymotrypsin; D011402:Pronase