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Fungi and Water
Published in Chuong Pham-Huy, Bruno Pham Huy, Food and Lifestyle in Health and Disease, 2022
Chuong Pham-Huy, Bruno Pham Huy
The cyclopeptide cyclosporine, also called cyclosporin A (CsA), was first isolated from the filamentous fungus (mold) Tolypocladium inflatum for its antifungal antibiotic and was later developed as an immunosuppressant drug in the early 1970s (148–150). This white mold was isolated from soil samples collected in Hardanger Vidda (Norway) and Wisconsin (USA) (150). CsA was first investigated as an antifungal antibiotic, but Borel et al. discovered its immunosuppressive activity in 1976, and it was approved for clinical use in 1983 (150). More than 30 analogs of CsA have been identified with different biological activities, including immunosuppressive, antifungal, antiviral, and antiparasitic properties (149).
Natural Products Structures and Analysis of the Cerrado Flora in Goiás
Published in Luzia Valentina Modolo, Mary Ann Foglio, Brazilian Medicinal Plants, 2019
Lucilia Kato, Vanessa Gisele Pasqualotto Severino, Aristônio Magalhães Teles, Aline Pereira Moraes, Vinicius Galvão Wakui, Núbia Alves Mariano Teixeira Pires Gomides, Rita de Cássia Lemos Lima, Cecilia Maria Alves de Oliveira
The cyclopeptide alkaloids are polyamide based composed of 13-, 14- or 15-membered macrocyclic rings in which a 10- or 12-membered peptide-type bridge spans the 1,3 or 1,4 positions of a benzene ring. Typically, the molecule contains two amino acids and one styrylamine unit. The 14-membered rings are more common kinds of cyclopeptides and contain four building blocks A (basic terminal end amino acid), B (β-hydroxyamino acid); C (a ring bonded amino acid taking part in the macrocycle ring) and D (hydroxylstyrylamine) as illustrated in Figure 11.11.
Shortcomings and Alternatives
Published in Willi Kullmann, Enzymatic Peptide Synthesis, 1987
Since it is unlikely that an autonomous, fully operative ex natura peptidyltransferase will be available within a reasonable space of time, attempts have been made to design and synthesize ex arte peptidyltransferases.31 These artificial enzymes have been designed both to accept as substrates the largest possible number of amino acid residues and to display their catalytic activities in organic solvents in order to favor proteosynthesis at the expense of proteolysis. The activity design of the presumptive synthetase mimetic peptide, which determined the relevant catalytic groups and their disposition in space,32 was based upon the active site of serine proteases represented by the triad Asp-Ser-His (cf. Chapter 4, Figure 3).33 These amino acid residues, the side-chain functions of which constitute a proton transfer system along hydrogen bonds, were integral parts of cyclosymmetric decapeptides (Figure 3). Conformationally cyclic peptides are less flexible than their linear counterparts and their relatively rigid shape not only improves the prospects of suitably positioned binding in relation to catalytic groups but also prevents the complete randomization of the peptidic backbone in the presence of denaturing agents. Consequently, cyclopeptides should be more resistant to the destabilizing effects of organic solvents which are known to reduce the biological activities of naturally occurring enzymes.
Current fatality rate of suspected cyclopeptide mushroom poisoning in the United States
Published in Clinical Toxicology, 2021
Jonathan De Olano, Josh J. Wang, Eric Villeneuve, Sophie Gosselin, Rana Biary, Mark K. Su, Robert S. Hoffman
Some mushrooms from the genera Amanita, Lepiota, Galerina and Conocybe contain toxic cyclopeptides. These toxins, often collectively called amatoxins, are potent inhibitors of RNA polymerase II [1]. Following ingestion of a toxic dose of amatoxin-containing mushrooms, patients typically present with delayed gastrointestinal symptoms that may progress to fulminant hepatic failure [2]. Reported fatality rates among patients who ingest cyclopeptide-containing mushrooms vary widely. One of the largest single series reported a fatality rate of over 22% in 205 clinical cases [3], and reported fatality rates ranged from 4.8% to 40% in one review [4]. In another review, the fatality rate with supportive care alone was reported at over 47% [2]. We recently reported that the fatality rate in one North American PCC’s experience was only 8.3% [5]. Although the exact explanation for this large variability in reported fatality rates is unknown, possible factors include geographic variations in toxicity, improvements in supportive care over time, and the variable use of a wide range of therapies. It is noteworthy that of all the proposed treatments for cyclopeptide mushroom poisoning, not a single one has been the subject of a randomized controlled trial in humans.
Quorum sensing inhibitors: a patent review (2014–2018)
Published in Expert Opinion on Therapeutic Patents, 2018
Xin Chen, Likun Zhang, Mingxiang Zhang, Huayu Liu, Panrui Lu, Kejiang Lin
Polypeptides are the most promising category of antagonists that act on the Agr system. One strategy to utilize them is to modify the natural peptide signal molecule. Blackwell et al. proposed that a cyclopeptide acts as a pan-group or group-selective inhibitor of the AgrC receptor. They also discovered that AgrC-1 agonist strongly inhibit the biofilm growth better effect than the natural AIP-1 [62]. Blackwell et al. also developed a series of AIP analogues to inhibit AgrC of S. epidermidis and alleviate its virulence. For instance, the compound n3LF (Figure 7) suppressed AgrC-IV activity, exhibiting an IC50 of 352 nM [63,64]. Shimizu et al. synthesized another cyclic peptide containing the sequence CFWAH (Figure 7). The cyclopeptide from the broth of Clostridium butyricum had a desired effect in terms of controlling the QS and virulence of Clostridium welchii. This specific compound suppressed VirS, regulated the expression of virulence genes and inhibited the downstream signal of the VirR/VirS system. In addition, AgrD from C. butyricum inhibited the production of Clostridium toxins [65].
Comment on “N-acetylcysteine as a treatment for amatoxin poisoning”
Published in Clinical Toxicology, 2021
Nicholas J. Connors, Sophie Gosselin, Robert S. Hoffman
In the most recent study, the case fatality rate of presumed cyclopeptide patients not treated with NAC was 2.75% [5]. We appreciate the difficulty in separating the potential benefit of NAC from the effects of confounders such as additional medications, gastrointestinal decontamination, extracorporeal treatments, and time to hospital presentation. While the evidence presented by the authors suggest that NAC has beneficial clinical effects controlled animal and in vitro studies suggested the opposite (no benefit) [6,7]. More granular human data would be helpful to bring this questions to a satisfactory conclusion, but an international registry of patients with cyclopeptide toxicity may be more feasible.