Sunflower trypsin inhibitor-1, proteolytic studies on a trypsin inhibitor peptide and its analogs

Colgrave, Michelle, Korsinczky, Michael Laszlo Jonas, Clark, Richard James, Foley, Fiona and Craik, David J. (2010). Sunflower trypsin inhibitor-1, proteolytic studies on a trypsin inhibitor peptide and its analogs. In: Proceedings of the 1st International Conference on Circular Proteins. 1st International Conference on Circular Proteins, Heron Island, Qld, Australia, (665-672). 18-21 October 2009. doi:10.1002/bip.21415

Author Colgrave, Michelle
Korsinczky, Michael Laszlo Jonas
Clark, Richard James
Foley, Fiona
Craik, David J.
Title of paper Sunflower trypsin inhibitor-1, proteolytic studies on a trypsin inhibitor peptide and its analogs
Conference name 1st International Conference on Circular Proteins
Conference location Heron Island, Qld, Australia
Conference dates 18-21 October 2009
Proceedings title Proceedings of the 1st International Conference on Circular Proteins   Check publisher's open access policy
Journal name Peptide Science   Check publisher's open access policy
Place of Publication Hoboken, N.J., U.S.
Publisher John Wiley & Sons
Publication Year 2010
Year available 2010
Sub-type Fully published paper
DOI 10.1002/bip.21415
Open Access Status Not yet assessed
ISSN 0006-3525
Volume 94
Issue 5
Start page 665
End page 672
Total pages 8
Language eng
Abstract/Summary Sunflower trypsin inhibitor-1 (SFTI-1) is a 14 amino acid cyclic peptide from sunflower seeds, which possesses exceptionally potent trypsin-inhibitory activity, and has promise as a stable peptide-based drug template. Within its compact structure, SFTI-1 combines a head-to-tail cyclized backbone and a disulfide bond. In this study, we synthesized a range of acyclic and disulfide-deficient analogs of SFTI-1 to investigate enzyme-assisted cyclization of the peptide backbone and proteolytic degradation that occurs as a result of incubation with trypsin. Electrospray and matrix-assisted laser desorption ionization mass spectrometry allowed the characterization of a range of novel degradation products and elucidation of the time-course for cyclization and/or proteolysis. Trypsin displayed the ability to resynthesize the scissile bond(s) and hence cyclize two of the linear permutants, whereas irreversible degradation was observed for another two permutants. An interesting ring contraction mediated by trypsin was observed, supporting a role for protease catalyzed splicing as a way of increasing the combinatorial diversity of cyclic peptides in nature. Disulfide-deficient mutants were degraded within minutes, emphasizing the critical role of the cysteine bridge in maintaining proteolytic stability of SFTI-1. Overall, the study provides additional support for the proposal that naturally occurring cyclic peptides like SFTI-1 are biosynthesized by proteolytic enzymes effectively catalyzing the reverse of their normal reaction to make, rather than break peptide bonds.
Keyword Circular Proteins
Cyclic Peptide
Bowman–Birk inhibitor
Trypsin Inhibitor
Mass Spectrometry
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Special Issue: Special Issue on International Conference on Circular Proteins. ** Published online 26 May 2010 in Wiley Online Library

Document type: Conference Paper
Sub-type: Fully published paper
Collections: Official 2011 Collection
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Created: Tue, 08 Feb 2011, 00:19:49 EST by Susan Allen on behalf of Institute for Molecular Bioscience