Natural structural diversity within a conserved cyclic peptide scaffold.
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.
Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia.
Alysha G
AG
Elliott
School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, 4072, Australia.
Bastian
B
Franke
School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, 4072, Australia.
David A
DA
Armstrong
Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia.
David J
DJ
Craik
Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia. joshua.mylne@uwa.edu.au.|School of Chemistry and Biochemistry and ARC Centre of Excellence in Plant Energy Biology, The University of Western Australia, Crawley, Perth, 6009, Australia. joshua.mylne@uwa.edu.au.
Joshua S
JS
Mylne
Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia. j.rosengren@uq.edu.au.|School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, 4072, Australia. j.rosengren@uq.edu.au.
K Johan
KJ
Rosengren
D000595:Amino Acid Sequence; D019659:Asteraceae / Q000737:chemistry; D017124:Conserved Sequence; D041961:Deuterium Exchange Measurement; D006368:Helianthus / Q000737:chemistry*; D006860:Hydrogen Bonding; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification; D010940:Plant Proteins / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification; D000072757:Protein Conformation, beta-Strand; D054730:Protein Interaction Domains and Motifs; D012639:Seeds / Q000737:chemistry*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D060327:Solid-Phase Synthesis Techniques; D055672:Static Electricity
D010456:Peptides, Cyclic; D010940:Plant Proteins; C448501:SFTI-1 peptide, sunflower
Cyclic peptide; PawS derived peptide (PDP); Peptide structure; Solution NMR spectroscopy; Sunflower trypsin inhibitor-1 (SFTI-1)