Amino Acids

, Volume 49, Issue 1, pp 103–116 | Cite as

Natural structural diversity within a conserved cyclic peptide scaffold

  • Alysha G. Elliott
  • Bastian Franke
  • David A. Armstrong
  • David J. Craik
  • Joshua S. Mylne
  • K. Johan Rosengren
Original Article


We recently isolated and described the evolutionary origin of a diverse class of small single-disulfide bonded peptides derived from Preproalbumin with SFTI-1 (PawS1) proteins in the seeds of flowering plants (Asteraceae). The founding member of the PawS derived peptide (PDP) family is the potent trypsin inhibitor SFTI-1 (sunflower trypsin inhibitor-1) from Helianthus annuus, the common sunflower. Here we provide additional structures and describe the structural diversity of this new class of small peptides, derived from solution NMR studies, in detail. We show that although most have a similar backbone framework with a single disulfide bond and in many cases a head-to-tail cyclized backbone, they all have their own characteristics in terms of projections of side-chains, flexibility and physiochemical properties, attributed to the variety of their sequences. Small cyclic and constrained peptides are popular as drug scaffolds in the pharmaceutical industry and our data highlight how amino acid side-chains can fine-tune conformations in these promising peptides.


Sunflower trypsin inhibitor-1 (SFTI-1) PawS derived peptide (PDP) Cyclic peptide Solution NMR spectroscopy Peptide structure 



Sunflower trypsin inhibitor-1


Preproalbumin with SFTI-1


PawS-derived peptide


Asparaginyl endopeptidase


Total correlation spectroscopy


Nuclear overhauser effect spectroscopy


Double quantum filtered correlation spectroscopy


Heteronuclear single quantum coherence spectroscopy


Reverse phase high performance liquid chromatography


Electrospray ionization mass spectrometry



A.G.E. and D.A. were awarded Australian Postgraduate Award Scholarships. D.J.C is an Australian Research Council (ARC) Laureate Fellow (FL150100146). J.S.M. and K.J.R. are ARC Future Fellows (FT120100013 and FT130100890 respectively). This work and B.F. were funded by an ARC Discovery Grant (DP120103369) to J.S.M. and K.J.R.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest. This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

726_2016_2333_MOESM1_ESM.pdf (836 kb)
Supplementary material 1 (PDF 837 kb)


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Copyright information

© Springer-Verlag Wien 2016

Authors and Affiliations

  • Alysha G. Elliott
    • 1
  • Bastian Franke
    • 2
  • David A. Armstrong
    • 2
  • David J. Craik
    • 1
  • Joshua S. Mylne
    • 1
    • 3
  • K. Johan Rosengren
    • 1
    • 2
  1. 1.Institute for Molecular BioscienceThe University of QueenslandBrisbaneAustralia
  2. 2.School of Biomedical SciencesThe University of QueenslandBrisbaneAustralia
  3. 3.School of Chemistry and Biochemistry and ARC Centre of Excellence in Plant Energy BiologyThe University of Western AustraliaCrawley, PerthAustralia

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