| 1. |
- Aboye, Teshome L., et al.
(författare)
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A Cactus-Derived Toxin-Like Cystine Knot Peptide with Selective Antimicrobial Activity
- 2015
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Ingår i: ChemBioChem. - : Wiley. - 1439-4227 .- 1439-7633. ; 16:7, s. 1068-1077
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Tidskriftsartikel (refereegranskat)abstract
- Naturally occurring cystine knot peptides show a wide range of biological activity, and as they have inherent stability they represent potential scaffolds for peptide-based drug design and biomolecular engineering. Here we report the discovery, sequencing, chemical synthesis, three-dimensional solution structure determination and bioactivity of the first cystine knot peptide from Cactaceae (cactus) family: Ep-AMP1 from Echinopsis pachanoi. The structure of Ep-AMP1 (35 amino acids) conforms to that of the inhibitor cystine knot (or knottin) family but represents a novel diverse sequence; its activity was more than 500 times higher against bacterial than against eukaryotic cells. Rapid bactericidal action and liposome leakage implicate membrane permeabilisation as the mechanism of action. Sequence homology places Ec-AMP1 in the plant C6-type of antimicrobial peptides, but the three dimensional structure is highly similar to that of a spider neurotoxin.
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| 2. |
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| 3. |
- Boldbaatar, Delgerbat, et al.
(författare)
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Synthesis, Structural Characterization, and Bioactivity of the Stable Peptide RCB-1 from Ricinus communis
- 2015
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Ingår i: Journal of natural products (Print). - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 78:11, s. 2545-2551
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Tidskriftsartikel (refereegranskat)abstract
- The Ricinus communis biomarker peptides RCB-1 to -3 comprise homologous sequences of 19 (RCB-1) or 18 (RCB-2 and -3) amino acid residues. They all include four cysteine moieties, which form two disulfide bonds. However, neither the 3D structure nor the biological activity of any of these peptides is known. The synthesis of RCB-1, using microwave-assisted, Fmoc-based solid-phase peptide synthesis, and a method for its oxidative folding are reported. The tertiary structure of RCB-1, subsequently established using solution-state NMR, reveals a twisted loop fold with antiparallel ?-sheets reinforced by the two disulfide bonds. Moreover, RCB-1 was tested for antibacterial, antifungal, and cytotoxic activity, as well as in a serum stability assay, in which it proved to be remarkably stable.
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| 4. |
- Burman, Robert, et al.
(författare)
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Chemistry and Biology of Cyclotides : Circular Plant Peptides Outside the Box
- 2014
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Ingår i: Journal of natural products (Print). - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 77:3, s. 724-736
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Forskningsöversikt (refereegranskat)abstract
- Cyclotides stand out as the largest family of circular proteins of plant origin hitherto known, with more than 280 sequences isolated at peptide level and many more predicted from gene sequences. Their unusual stability resulting from the signature cyclic cystine knot (CCK) motif has triggered a broad interest in these molecules for potential therapeutic and agricultural applications. Since the time of the first cyclotide discovery, our laboratory in Uppsala has been engaged in cyclotide discovery as well as the development of protocols to isolate and characterize these seamless peptides. We have also developed methods to chemically synthesize cyclotides by Fmoc-SPPS, which are useful in protein grafting applications. In this review, experience in cyclotide research over two decades and the recent literature related to their structures, synthesis, and folding as well the recent proof-of-concept findings on their use as "epitope" stabilizing scaffolds are summarized.
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| 5. |
- Cárdenas, Paco, 1976-, et al.
(författare)
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Good Practices in Sponge Natural Product Studies : Revising Vouchers with Isomalabaricane Triterpenes
- 2022
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Ingår i: Marine Drugs. - : MDPI. - 1660-3397. ; 20:3
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Tidskriftsartikel (refereegranskat)abstract
- Species misidentification in the field of natural products is an acknowledged problem. These errors are especially widespread in sponge studies, albeit rarely assessed and documented. As a case study, we aim to revisit reports of isomalabaricane triterpenes, isolated from four demosponge genera: Jaspis, Geodia, Stelletta and Rhabdastrella. From a total of 44 articles (1981-2022), 27 unique vouchers were listed, 21 of which were accessed and re-examined here: 11 (52.4%) of these were misidentified. Overall, 65.9% of the studies published an incorrect species name: previously identified Jaspis and Stelletta species were all in fact Rhabdastrella globostellata. We conclude that isomalabaricane triterpenes were isolated from only two Rhabdastrella species and possibly one Geodia species. In addition to shedding a new light on the distribution of isomalabaricane triterpenes, this study is an opportunity to highlight the crucial importance of vouchers in natural product studies. Doing so, we discuss the impact of species misidentification and poor accessibility of vouchers in the field of sponge natural products. We advocate for stricter voucher guidelines in natural product journals and propose a common protocol of good practice, in the hope of reducing misidentifications in sponge studies, ensure reproducibility of studies, and facilitate follow-up work on the original material.
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| 6. |
- Carstens, Bodil B., et al.
(författare)
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Isolation, characterization, and synthesis of the Barrettides : disulfide-containing peptides from the marine sponge Geodia barretti
- 2015
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Ingår i: Journal of Natural Products. - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 78:8, s. 1886-1893
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Tidskriftsartikel (refereegranskat)abstract
- Two disulfide-containing peptides, barrettides A (1) and B (2), from the cold-water marine sponge Geodia barretti are described. Those 31 amino acid residue long peptides were sequenced using mass spectrometry methods and structurally characterized using NMR spectroscopy. The structure of 1 was confirmed by total synthesis using the solid-phase peptide synthesis approach that was developed. The two peptides were found to differ only at a single position in their sequence. The three-dimensional structure of 1 revealed that these peptides possess a unique fold consisting of a long β-hairpin structure that is cross-braced by two disulfide bonds in a ladder-like arrangement. The peptides are amphipathic in nature with the hydrophobic and charged residues clustered on separate faces of the molecule. The barrettides were found not to inhibit the growth of either Escherichia coli or Staphylococcus aureus but displayed antifouling activity against barnacle larvae (Balanus improvisus) without lethal effects in the concentrations tested. (Figure Presented).
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| 7. |
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| 8. |
- Eriksson, Camilla, 1986-
(författare)
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Cyclic peptides as biological tools : Applications for diagnosis and therapeutics in rheumatoid arthritis and COVID-19
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall aims of the projects included in this thesis were to design, synthesize and evaluate cyclic peptide scaffolds grafted with biological epitopes for their ability to bind antibodies in rheumatoid arthritis and COVID-19 sera. One of the main outcomes of this thesis was the observation that scaffold peptides grafted with target epitopes efficiently neutralized anti-citrullinated protein autoantibodies (ACPA) from rheumatoid arthritis patients. Another main outcome was that grafted cyclic scaffold peptides demonstrated potential for use in COVID-19 diagnostics.In paper I and II, peptides grafted with epitopes from reported ACPA target proteins were designed, synthesized and evaluated for ACPA-neutralizing activity. Cyclic scaffold peptides and linear peptides were compared. In paper I, we demonstrate that the peptides based on the stable scaffold sunflower trypsin inhibitor-1 (SFTI-1) can be used to neutralize ACPA. The peptides s[Cit-Fil](306-323), s[Cit-Vim](60-75) and s[Cit-Vim](2-17) were particularly efficient, and blocked 80-93% with IC50-values ranging from 5.6 -82 µM. Moreover we show that compared to their linear counterparts, these peptides demonstrated enhanced stability in human serum.In paper II, scaffold peptides from the PDP-family (PawS-derived peptides) with different structural properties were evaluated for ACPA-neutralizing activity. By grafting the same ACPA target epitope on three PDP-peptides, their impact on antibody binding could be compared to the linear epitope and to an SFTI-grafted epitope. No substantial difference in antibody binding was contributed by the scaffolds, but a reduction in background was observed for the PDP-peptides when compared to the SFTI-1-peptide. The peptides demonstrated enhanced serum stability in vitro.In Paper III, grafted SFTI-1-scaffold peptides were applied to COVID-19 antibody detection. SFTI-1 was grafted with immunodominant epitopes from SARS-CoV-2 virus spike protein. Epitopes in linear form were synthesized for comparison. A SARS-CoV-2 ELISA was developed and a cohort of positive and negative samples were tested for anti-SARS-CoV-2 reactivity. The peptide (S2_1146-1161_c) stood out as a promising antigen and recognized positive and negative sera with similar capacity as both a lateral flow test and a commercial SARS-CoV-2 ELISA. In paper IV, cyclic scaffold peptides grafted with epitopes from SARS-CoV-2 proved useful in an antibody proximity extension assay, both at detecting and distinguishing COVID-19 positive and negative sera.
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| 9. |
- Eriksson, Camilla, et al.
(författare)
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Epitopes displayed in a cyclic peptide scaffold bind SARS-CoV-2 antibodies
- 2023
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Ingår i: ChemBioChem. - : Wiley-VCH Verlagsgesellschaft. - 1439-4227 .- 1439-7633. ; 24:15
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Tidskriftsartikel (refereegranskat)abstract
- The SARS-CoV-2 virus that causes COVID-19 is a global health issue. The spread of the virus has resulted in seven million deaths to date. The emergence of new viral strains highlights the importance of continuous surveillance of the SARS-CoV-2 virus by using timely and accurate diagnostic tools. Here, we used a stable cyclic peptide scaffolds to present antigenic sequences derived from the spike protein that are reactive to SARS-CoV-2 antibodies. Using peptide sequences from different domains of SARS-CoV-2 spike proteins, we grafted epitopes on the peptide scaffold sunflower trypsin inhibitor 1 (SFTI-1). These scaffold peptides were then used to develop an ELISA to detect SARS-CoV-2 antibodies in serum. We show that displaying epitopes on the scaffold improves reactivity overall. One of the scaffold peptides (S2_1146-1161_c) has reactivity equal to that of commercial assays, and shows diagnostic potential.
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| 10. |
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