The structure of well-folded β-hairpin peptides promotes resistance to peptidase degradation

✍ Scribed by Lauren L. Cline; Marcey L. Waters

• Publisher: Wiley (John Wiley & Sons)
• Year: 2009
• Tongue: English
• Weight: 259 KB
• Volume: 92
• Category: Article
• ISSN: 0006-3525
• DOI: 10.1002/bip.21266

✦ Synopsis

Abstract

To investigate the effect of peptide secondary structure on proteolytic resistance, we have synthesized a series of peptides based on a well‐folded β‐hairpin, WKWK. Mutations were made within the peptide which either decreased or increased the propensity to form β‐hairpin structures and one scrambled sequence was used as an unstructured control. The peptides were incubated with three different enzymes, α‐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 β‐turn resulted in the most proteolytic resistant peptides. The results from this study suggest that β‐hairpin structure is a viable way to provide added protease resistance to a peptide. © 2009 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 92: 502–507, 2009.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at [email protected]