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Natural structural diversity within a conserved cyclic peptide scaffold

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Abstract

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.

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Abbreviations

SFTI-1:

Sunflower trypsin inhibitor-1

PawS1:

Preproalbumin with SFTI-1

PDP:

PawS-derived peptide

AEP:

Asparaginyl endopeptidase

TOCSY:

Total correlation spectroscopy

NOESY:

Nuclear overhauser effect spectroscopy

DQF-COSY:

Double quantum filtered correlation spectroscopy

HSQC:

Heteronuclear single quantum coherence spectroscopy

RP-HPLC:

Reverse phase high performance liquid chromatography

ESI-MS:

Electrospray ionization mass spectrometry

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Acknowledgments

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.

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Authors and Affiliations

  1. Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia

    Alysha G. Elliott, David J. Craik, Joshua S. Mylne & K. Johan Rosengren

  2. School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, 4072, Australia

    Bastian Franke, David A. Armstrong & K. Johan Rosengren

  3. School of Chemistry and Biochemistry and ARC Centre of Excellence in Plant Energy Biology, The University of Western Australia, Crawley, Perth, 6009, Australia

    Joshua S. Mylne

Authors
  1. Alysha G. Elliott
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  2. Bastian Franke
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  3. David A. Armstrong
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  4. David J. Craik
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  5. Joshua S. Mylne
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  6. K. Johan Rosengren
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Correspondence to Joshua S. Mylne or K. Johan Rosengren.

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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.

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Handling Editor: J. Bode.

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Elliott, A.G., Franke, B., Armstrong, D.A. et al. Natural structural diversity within a conserved cyclic peptide scaffold. Amino Acids 49, 103–116 (2017). https://doi.org/10.1007/s00726-016-2333-x

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