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David J. Craik - One of the best experts on this subject based on the ideXlab platform.

  • Backbone Cyclised Peptides from Plants Show Molluscicidal Activity against the Rice Pest Pomacea canaliculata (Golden Apple Snail)
    Journal of agricultural and food chemistry, 2008
    Co-Authors: Manuel R. Plan, Ivana Saska, Arsenia G. Cagauan, David J. Craik
    Abstract:

    Golden apple snails (Pomacea canaliculata) are serious pests of rice in South East Asia. Cyclotides are backbone cyclized peptides produced by plants from Rubiaceae and Violaceae. In this study, we investigated the molluscicidal activity of cyclotides against golden apple snails. Crude cyclotide extracts from both Oldenlandia affinis and Viola Odorata plants showed molluscicidal activity comparable to the synthetic molluscicide metaldehyde. Individual cyclotides from each extract demonstrated a range of molluscicidal activities. The cyclotides cycloViolacin O1, kalata B1, and kalata B2 were more toxic to golden apple snails than metaldehyde, while kalata B7 and kalata B8 did not cause significant mortality. The toxicity of the cyclotide kalata B2 on a nontarget species, the Nile tilapia (Oreochromis niloticus), was three times lower than the common piscicide rotenone. Our findings suggest that the existing diversity of cyclotides in plants could be used to develop natural molluscicides.

  • a novel suite of cyclotides from Viola Odorata sequence variation and the implications for structure function and stability
    Biochemical Journal, 2006
    Co-Authors: David Ireland, Michelle L Colgrave, David J. Craik
    Abstract:

    Cyclotides are a fascinating family of plant-derived peptides characterized by their head-to-tail cyclized backbone and knotted arrangement of three disulfide bonds. This conserved structural architecture, termed the CCK (cyclic cystine knot), is responsible for their exceptional resistance to thermal, chemical and enzymatic degradation. Cyclotides have a variety of biological activities, but their insecticidal activities suggest that their primary function is in plant defence. In the present study, we determined the cyclotide content of the sweet violet Viola Odorata, a member of the Violaceae family. We identified 30 cyclotides from the aerial parts and roots of this plant, 13 of which are novel sequences. The new sequences provide information about the natural diversity of cyclotides and the role of particular residues in defining structure and function. As many of the biological activities of cyclotides appear to be associated with membrane interactions, we used haemolytic activity as a marker of bioactivity for a selection of the new cyclotides. The new cyclotides were tested for their ability to resist proteolysis by a range of enzymes and, in common with other cyclotides, were completely resistant to trypsin, pepsin and thermolysin. The results show that while biological activity varies with the sequence, the proteolytic stability of the framework does not, and appears to be an inherent feature of the cyclotide framework. The structure of one of the new cyclotides, cycloViolacin O14, was determined and shown to contain the CCK motif. This study confirms that cyclotides may be regarded as a natural combinatorial template that displays a variety of peptide epitopes most likely targeted to a range of plant pests and pathogens.

  • discovery and characterization of a linear cyclotide from Viola Odorata implications for the processing of circular proteins
    Journal of Molecular Biology, 2006
    Co-Authors: David Ireland, Michelle L Colgrave, Philip Nguyencong, Norelle L Daly, David J. Craik
    Abstract:

    Cyclotides are mini-proteins of 28-37 amino acid residues that have the unusual feature of a head-to-tail cyclic backbone surrounding a cystine knot. This molecular architecture gives the cyclotides heightened resistance to thermal, chemical and enzymatic degradation and has prompted investigations into their use as scaffolds in peptide therapeutics. There are now more than 80 reported cyclotide sequences from plants in the families Rubiaceae, Violaceae and Cucurbitaceae, with a wide variety of biological activities observed. However, potentially limiting the development of cyclotide-based therapeutics is a lack of understanding of the mechanism by which these peptides are cyclized in vivo. Until now, no linear versions of cyclotides have been reported, limiting our understanding of the cyclization mechanism. This study reports the discovery of a naturally occurring linear cyclotide, Violacin A, from the plant Viola Odorata and discusses the implications for in vivo cyclization of peptides. The elucidation of the cDNA clone of Violacin A revealed a point mutation that introduces a stop codon, which inhibits the translation of a key Asn residue that is thought to be required for cyclization. The three-dimensional solution structure of Violacin A was determined and found to adopt the cystine knot fold of native cyclotides. Enzymatic stability assays on Violacin A indicate that despite an increase in the flexibility of the structure relative to cyclic counterparts, the cystine knot preserves the overall stability of the molecule. (c) 2006 Elsevier Ltd. All rights reserved.

  • conserved structural and sequence elements implicated in the processing of gene encoded circular proteins
    Journal of Biological Chemistry, 2004
    Co-Authors: Julie L Dutton, Norelle L Daly, Rosemary Renda, Clement Waine, Richard J Clark, Cameron Victor Jennings, Marilyn A Anderson, David J. Craik
    Abstract:

    Abstract The cyclotides are the largest family of naturally occurring circular proteins. The mechanism by which the termini of these gene-encoded proteins are linked seamlessly with a peptide bond to form a circular backbone is unknown. Here we report cyclotide-encoding cDNA sequences from the plant Viola Odorata and compare them with those from an evolutionarily distinct species, Oldenlandia affinis. Individual members of this multigene family encode one to three mature cyclotide domains. These domains are preceded by N-terminal repeat regions (NTRs) that are conserved within a plant species but not between species. We have structurally characterized peptides corresponding to these NTRs and show that, despite them having no sequence homology, they form a structurally conserved α-helical motif. This structural conservation suggests a vital role for the NTR in the in vivo folding, processing, or detoxification of cyclotide domains from the precursor protein.

  • Variations in Cyclotide Expression in Viola Species
    Journal of Natural Products, 2004
    Co-Authors: Manuela Trabi, Erika Svangård, Anders Herrmann, Per Claeson, David J. Craik, Ulf Göransson, Lars Bohlin
    Abstract:

    Cyclotides, a family of approximately 50 mini-proteins isolated from various Violaceae and Rubiaceae plants, are characterized by their circular peptide backbone and six conserved cysteine residues arranged in a cystine knot motif. Cyclotides show a wide range of biological activities, making them interesting targets for both pharmaceutical and agrochemical research, but little is known about their natural function and the events that trigger their expression. An investigation of the geographical and seasonal variations of cyclotide profiles has been performed, using the native Australian violet, Viola hederacea, and the Swedish sweet violet, Viola Odorata, as model plants. The results showed that in the Australian violet the relative peptide levels of some cyclotides remained almost constant throughout the year, while other cyclotides were present only at certain times of the year. Therefore, it appears that V. hederacea expresses a basic armory of cyclotides as well as special add-ons whose levels are influenced by external factors. In the Swedish violet, cyclotide levels were increased up to 14 times during the warmest period of the year. The larger variation in expression levels of the Swedish plants may be a reflection of a greater climatic variation.

S N C Sridhar - One of the best experts on this subject based on the ideXlab platform.

  • fungal endophytes associated with Viola Odorata linn as bioresource for pancreatic lipase inhibitors
    BMC Complementary and Alternative Medicine, 2017
    Co-Authors: M. Katoch, Atish T Paul, G Singh, S N C Sridhar
    Abstract:

    As per the recent statistical reports of World Health Organisation (WHO), 13% of total global population is obese. Orlistat remains to be the only drug approved for the long term treatment of obesity. Recent findings highlighted severe adverse effects of orlistat that included hepatotoxicity, gall stones, kidney stones and acute pancreatitis. Therefore, search for new drug is required. The investigations based on endophytic natural products would prove pivotal in the global fight against this health issue. Obesity is associated with lipid metabolism involving pancreatic lipase enzyme. The inhibition of pancreatic lipase is demonstrated by using the extracts of endophytes isolated from Viola Odorata Linn. In addition, endophytes were identified using ITS based rDNA sequencing. Present study involves the isolation and identification of 27 endophytes from V. Odorata. All the endophytes were evaluated for lipase inhibitory activities. The extracts of seven endophytes exhibited lipase inhibitory activity with IC50 < 10 μg/mL. The extract of VOLF4 (Aspergillus sp.) displayed promising lipase inhibitory activity (IC50 3.8 μg/mL). The present study demonstrates that V. Odorata harbors endophytic community with potent lipase inhibitory activity. VOLF4 is the potential endophyte. The extract of VOLF4 can be used to develop the potential drug to treat obesity.

  • Fungal endophytes associated with Viola Odorata Linn. as bioresource for pancreatic lipase inhibitors
    BMC Complementary and Alternative Medicine, 2017
    Co-Authors: M. Katoch, G Singh, A. Paul, S N C Sridhar
    Abstract:

    Background As per the recent statistical reports of World Health Organisation (WHO), 13% of total global population is obese. Orlistat remains to be the only drug approved for the long term treatment of obesity. Recent findings highlighted severe adverse effects of orlistat that included hepatotoxicity, gall stones, kidney stones and acute pancreatitis. Therefore, search for new drug is required. The investigations based on endophytic natural products would prove pivotal in the global fight against this health issue. Methods Obesity is associated with lipid metabolism involving pancreatic lipase enzyme. The inhibition of pancreatic lipase is demonstrated by using the extracts of endophytes isolated from Viola Odorata Linn. In addition, endophytes were identified using ITS based rDNA sequencing. Results Present study involves the isolation and identification of 27 endophytes from V. Odorata. All the endophytes were evaluated for lipase inhibitory activities. The extracts of seven endophytes exhibited lipase inhibitory activity with IC_50 

Berling E. - One of the best experts on this subject based on the ideXlab platform.

  • Obtention de clones de violettes (Viola Odorata) indemnes de virus par culture d'apex méristématique
    'EDP Sciences', 1997
    Co-Authors: Van Caneghem A., Poupet Alain, Beck D., Berling E.
    Abstract:

    National audienceThe production of sweet violet (Viola Odorata var victoria) on the French Riviera is severely and increasingly damaged by a frequent complex of three viruses: cucumber mosaic virus, bean yellow mosaic virus and Viola mottle virus. In this paper a complete scheme for obtaining virus free plants from meristem tip culture is described: - the formulation of a medium containing kinetin, gibberellic acid and indolylacetic acid for the isolation of the meristem tips, the best growth being observed in stirred liquid conditions; - the subsequent propagation through axillary budding by using agar solidified medium containing N6-benzylaminopurin; - the final rooting of plantlets with a low auxin level and their acclimatization in a perlite-peat mixture. Biological and serological tests allowed the identification of two virus free clones which are intensively multiplied. They will be later transferred to a greenhouse protected against the aphid vectors.Les plantations locales de violettes (Viola Odorata var victoria) sont fréquemment contaminées par plusieurs virus : virus de la mosaïque du concombre, de la mosaïque jaune du haricot, Viola mottle virus, dont les dommages croissants menacent la qualité de la production et sa pérennité. Nous décrivons dans cette étude une méthode complète de « régénération » des clones de violette virosés par culture d’apex méristématique : isolement et développement des explants primaires en conditions liquides agitées avec des milieux de culture renfermant de la kinétine, de l’acide gibbérellique et de l’acide indol-acétique ; multiplication végétative par bourgeonnement axillaire dans des milieux de culture solides enrichis en N6-benzylaminopurine ; enracinement en présence de faibles concentrations d’auxine et acclimatation des vitroplants obtenus dans un substrat tourbe-perlite. Des épreuves d’état sanitaire, biologique et immunologique, appliquées aux clones obtenus ont permis l’isolement de deux clones apparemment indemnes de virus qui sont actuellement rapidement multipliés en vue de la reconstitution des plantations. Cette démarche est indissociable des mesures prophylactiques pour limiter la recontamination des plants par les insectes vecteurs

  • Obtention de clones de violettes (Viola Odorata) indemnes de virus par culture d'apex méristématique
    1997
    Co-Authors: Van Caneghem A., Beck D., Poupet A., Berling E.
    Abstract:

    Les plantations locales de violettes (Viola Odorata var victoria) sont fréquemment contaminées par plusieurs virus : virus de la mosaïque du concombre, de la mosaïque jaune du haricot, Viola mottle virus, dont les dommages croissants menacent la qualité de la production et sa pérennité. Nous décrivons dans cette étude une méthode complète de « régénération » des clones de violette virosés par culture d’apex méristématique : isolement et développement des explants primaires en conditions liquides agitées avec des milieux de culture renfermant de la kinétine, de l’acide gibbérellique et de l’acide indol-acétique ; multiplication végétative par bourgeonnement axillaire dans des milieux de culture solides enrichis en N6-benzylaminopurine ; enracinement en présence de faibles concentrations d’auxine et acclimatation des vitroplants obtenus dans un substrat tourbe-perlite. Des épreuves d’état sanitaire, biologique et immunologique, appliquées aux clones obtenus ont permis l’isolement de deux clones apparemment indemnes de virus qui sont actuellement rapidement multipliés en vue de la reconstitution des plantations. Cette démarche est indissociable des mesures prophylactiques pour limiter la recontamination des plants par les insectes vecteurs.The production of sweet violet (Viola Odorata var victoria) on the French Riviera is severely and increasingly damaged by a frequent complex of three viruses: cucumber mosaic virus, bean yellow mosaic virus and Viola mottle virus. In this paper a complete scheme for obtaining virus free plants from meristem tip culture is described: - the formulation of a medium containing kinetin, gibberellic acid and indolylacetic acid for the isolation of the meristem tips, the best growth being observed in stirred liquid conditions; - the subsequent propagation through axillary budding by using agar solidified medium containing N6-benzylaminopurin; - the final rooting of plantlets with a low auxin level and their acclimatization in a perlite-peat mixture. Biological and serological tests allowed the identification of two virus free clones which are intensively multiplied. They will be later transferred to a greenhouse protected against the aphid vectors

M. Katoch - One of the best experts on this subject based on the ideXlab platform.

  • fungal endophytes associated with Viola Odorata linn as bioresource for pancreatic lipase inhibitors
    BMC Complementary and Alternative Medicine, 2017
    Co-Authors: M. Katoch, Atish T Paul, G Singh, S N C Sridhar
    Abstract:

    As per the recent statistical reports of World Health Organisation (WHO), 13% of total global population is obese. Orlistat remains to be the only drug approved for the long term treatment of obesity. Recent findings highlighted severe adverse effects of orlistat that included hepatotoxicity, gall stones, kidney stones and acute pancreatitis. Therefore, search for new drug is required. The investigations based on endophytic natural products would prove pivotal in the global fight against this health issue. Obesity is associated with lipid metabolism involving pancreatic lipase enzyme. The inhibition of pancreatic lipase is demonstrated by using the extracts of endophytes isolated from Viola Odorata Linn. In addition, endophytes were identified using ITS based rDNA sequencing. Present study involves the isolation and identification of 27 endophytes from V. Odorata. All the endophytes were evaluated for lipase inhibitory activities. The extracts of seven endophytes exhibited lipase inhibitory activity with IC50 < 10 μg/mL. The extract of VOLF4 (Aspergillus sp.) displayed promising lipase inhibitory activity (IC50 3.8 μg/mL). The present study demonstrates that V. Odorata harbors endophytic community with potent lipase inhibitory activity. VOLF4 is the potential endophyte. The extract of VOLF4 can be used to develop the potential drug to treat obesity.

  • Fungal endophytes associated with Viola Odorata Linn. as bioresource for pancreatic lipase inhibitors
    BMC Complementary and Alternative Medicine, 2017
    Co-Authors: M. Katoch, G Singh, A. Paul, S N C Sridhar
    Abstract:

    Background As per the recent statistical reports of World Health Organisation (WHO), 13% of total global population is obese. Orlistat remains to be the only drug approved for the long term treatment of obesity. Recent findings highlighted severe adverse effects of orlistat that included hepatotoxicity, gall stones, kidney stones and acute pancreatitis. Therefore, search for new drug is required. The investigations based on endophytic natural products would prove pivotal in the global fight against this health issue. Methods Obesity is associated with lipid metabolism involving pancreatic lipase enzyme. The inhibition of pancreatic lipase is demonstrated by using the extracts of endophytes isolated from Viola Odorata Linn. In addition, endophytes were identified using ITS based rDNA sequencing. Results Present study involves the isolation and identification of 27 endophytes from V. Odorata. All the endophytes were evaluated for lipase inhibitory activities. The extracts of seven endophytes exhibited lipase inhibitory activity with IC_50 

Christine L Kirkpatrick - One of the best experts on this subject based on the ideXlab platform.

  • pepsavi ms reveals anticancer and antifungal cycloViolacins in Viola Odorata
    Phytochemistry, 2018
    Co-Authors: Nicole C Parsley, Christine L Kirkpatrick, Christopher M Crittenden, Javad Ghassemi Rad, David W Hoskin, Jennifer S Brodbelt, Leslie M Hicks
    Abstract:

    Widespread resistance to antimicrobial and cancer therapeutics is evolving in every country worldwide and has a direct impact on global health, agriculture and the economy. The specificity and selectivity of bioactive peptide natural products present a possible stopgap measure to address the ongoing deficit of new therapeutic compounds. PepSAVI-MS (Statistically-guided bioActive Peptides prioritized VIa Mass Spectrometry) is an adaptable method for the analysis of natural product libraries to rapidly identify bioactive peptides. This pipeline was validated via screening of the cyclotide-rich botanical species Viola Odorata and identification of the known antimicrobial and anticancer cyclotide cycloViolacin O2. Herein we present and validate novel bioactivities of the anthelmintic V. Odorata cyclotide, cycloViolacin O8 (cyO8), including micromolar anticancer activity against PC-3 prostate, MDA-MB-231 breast, and OVCAR-3 ovarian cancer cell lines and antifungal activity against the agricultural pathogen Fusarium graminearum. A reduction/alkylation strategy in tandem with PepSAVI-MS analysis also revealed several previously uncharacterized putatively bioactive cyclotides. Downstream implementation of ultraviolet photodissociation (UVPD) tandem mass spectrometry is demonstrated for cyO8 as a method to address traditionally difficult-to-sequence cyclotide species. This work emphasizes the therapeutic and agricultural potential of natural product bioactive peptides and the necessity of developing robust analytical tools to deconvolute nature's complexity.

  • the pepsavi ms pipeline for natural product bioactive peptide discovery
    Analytical Chemistry, 2017
    Co-Authors: Christine L Kirkpatrick, Elijah N Mccool, Evan W Mcconnell, David A Pritchard, Michael Hebert, Renee Fleeman, Jessie Adams, Christopher A Broberg, Alex Chao, Amer Jamil
    Abstract:

    The recent increase in extensively drug-resistant bacterial pathogens and the associated increase of morbidity and mortality demonstrate the immediate need for new antibiotic backbones with novel mechanisms of action. Here, we report the development of the PepSAVI-MS pipeline for bioactive peptide discovery. This highly versatile platform employs mass spectrometry and statistics to identify bioactive peptide targets from complex biological samples. We validate the use of this platform through the successful identification of known bioactive peptides from a botanical species, Viola Odorata. Using this pipeline, we have widened the known antimicrobial spectrum for V. Odorata cyclotides, including antibacterial activity of cycloViolacin O2 against A. baumannii. We further demonstrate the broad applicability of the platform through the identification of novel anticancer activities for cycloViolacins by their cytotoxicity against ovarian, breast, and prostate cancer cell lines.