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Natural structural diversity within a conserved cyclic peptide scaffold
- Elliott, Alysha G., Franke, Bastian, Armstrong, David A., Craik, David J., Mylne, Joshua S., Rosengren, K. Johan
- Amino acids 2017 v.49 no.1 pp. 103-116
- Helianthus annuus, amino acids, disulfide bonds, drugs, nuclear magnetic resonance spectroscopy, peptides, pharmaceutical industry, proteins, seeds, trypsin, trypsin inhibitors
- 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.