Oral Presentation 6th Modern Solid Phase Peptide Synthesis & Its Applications Symposium 2017

A family of cyclic peptides hidden within seed storage albumin precursors with applications in drug design (#20)

Johan Rosengren 1 , Bastian Franke 1 , Joshua Mylne 2
  1. University of Queensland, Brisbane, QLD, Australia
  2. University of Western Australia, Perth, WA, Australia

Seed storage albumins are degraded during germination to provide nutrients for the developing seedling. An unusual seed storage albumin precursor found in the common sunflower Helianthus annuus contains a 14-residue sequence insert with a single disulfide bond that during the proteolytic processing is cleaved out and head-to-tail cyclized. The resultant cyclic peptide is a sub-nanomolar trypsin inhibitor known as Sunflower Trypsin Inhibitor-1, SFTI-1. Screening ventures using both genetic and LC-MS strategies have now shown that SFTI-1 is only one member of a large family of related cyclic peptides produced from albumin precursors in different plants of the Asteraceae family. These peptides are readily produced by solid phase peptide synthesis allowing structural studies using solution NMR spectroscopy. The peptides, which are diverse in sequence apart from a conserved disulfide bond, adopt a range of different folds with different physiochemical characteristics. Sequences that are closely related to SFTI-1 are also capable of inhibiting trypsin, while the functional significance of the more distantly related peptides is yet to be understood. However, recent success with grafting bioactive epitopes into SFTI-1 suggest this diverse family represent a collection of scaffolds suitable for stabilizing different sequences and providing different characteristics for peptide drug leads.