| 1. |
- Payne, Colton D., et al.
(författare)
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Solution NMR and racemic crystallography provide insights into a novel structural class of cyclic plant peptides
- 2021
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Ingår i: RSC CHEMICAL BIOLOGY. - : Royal Society of Chemistry. - 2633-0679. ; 2:6, s. 1682-1691
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Tidskriftsartikel (refereegranskat)abstract
- Head-to-tail cyclic and disulfide-rich peptides are natural products with applications in drug design. Among these are the PawS-Derived Peptides (PDPs) produced in seeds of the daisy plant family. PDP-23 is a unique member of this class in that it is twice the typical size and adopts two beta-hairpins separated by a hinge region. The beta-hairpins, both stabilised by a single disulfide bond, fold together into a V-shaped tertiary structure creating a hydrophobic core. In water two PDP-23 molecules merge their hydrophobic cores to form a square prism quaternary structure. Here, we synthesised PDP-23 and its enantiomer comprising d-amino acids and achiral glycine, which allowed us to confirm these solution NMR structural data by racemic crystallography. Furthermore, we discovered the related PDP-24. NMR analysis showed that PDP-24 does not form a dimeric structure and it has poor water solubility, but in less polar solvents adopts near identical secondary and tertiary structure to PDP-23. The natural role of these peptides in plants remains enigmatic, as we did not observe any antimicrobial or insecticidal activity. However, the plasticity of these larger PDPs and their ability to change structure under different conditions make them appealing peptide drug scaffolds.
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| 2. |
- Herrmann, Anders, et al.
(författare)
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The alpine violet, Viola biflora, is a rich source of novel cyclotides with potent cytotoxic cytotoxicity
- 2008
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Ingår i: Phytochemistry. - : Elsevier BV. - 0031-9422 .- 1873-3700. ; 69:4, s. 939-952
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Tidskriftsartikel (refereegranskat)abstract
- The cyclotides are currently the largest known family of head-to-tail cyclic proteins. The complex structure of these small plant proteins, which consist of approximately 30 amino acid residues, contains both a circular peptide backbone and a cystine knot, the combination of which produces the cyclic cystine knot motif. To date, cyclotides have been found in plants from the Rubiaceae, Violaceace and Cucurbitaceae families, and are believed to be part of the host defence system. In addition to their insecticidal effect, cyclotides have also been shown to be cytotoxic, anti-HIV, antimicrobial and haemolytic agents. In this study, we show that the alpine violet Viola biflora (Violaceae) is a rich source of cyclotides. The sequences of 11 cyclotides, vibi A-K, were determined by isolation and MS/MS sequencing of proteins and screening of a cDNA library of V. biflora in parallel. For the cDNA screening, a degenerate primer against a conserved (AAFALPA) motif in the cyclotide precursor ER signal sequence yielded a series of predicted cyclotide sequences that were correlated to those of the isolated proteins. There was an apparent discrepancy between the results of the two strategies as only one of the isolated proteins could be identified as a cDNA clone. Finally, to correlate amino acid sequence to cytotoxic potency, vibi D, E, G and H were analysed using a fluorometric microculture cytotoxicity assay using a lymphoma cell line. The IC50-values of the bracelet cyclotides vibi E, G and H ranged between 0.96 and 5.0 mu M while the Mobius cyclotide vibi D was not cytotoxic at 30 mu M.
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