The insecticidal potential of venom peptides

Smith, Jennifer J.; Herzig, Volker; King, Glenn F.; Alewood, Paul F.

doi:10.1007/s00018-013-1315-3

Cited by 99 publications

(88 citation statements)

References 206 publications

(300 reference statements)

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“…The absence of activity of these ␦-conotoxins on the insect Na v channel contrasts with activity seen with Na v channel-targeting toxins from other venomous animals such as scorpions or spiders, which typically display higher potencies against insect channels than against the mammalian Na v channel isoforms (20). No activity for ␦-CnVIB, ␦-CnVIC, or ␦-CnVID (1 M) was observed on the potassium channels K v 1.1, K v 1.3, K v 1.4, K v 1.5, Shaker IR, and hERG (data not shown).…”

Section: Purification Of 3 Novel ␦-Conotoxins From Crude Venom-mentioning

confidence: 92%

δ-Conotoxins Synthesized Using an Acid-cleavable Solubility Tag Approach Reveal Key Structural Determinants for NaV Subtype Selectivity

Peigneur

Paolini-Bertrand

Gaertner

et al. 2014

Journal of Biological Chemistry

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Background: Conotoxins are marine snail venom peptides of interest as pharmacological tools and potential medicines. Results: ␦-Conotoxins are poorly understood because they are difficult to synthesize. Using a new synthesis approach, we readily produced three ␦-conotoxins and two analogs, obtaining new pharmacological insights. Conclusion: Key structures on ␦-conotoxins determine Na V subtype selectivity. Significance: Our synthesis approach is applicable to other similarly challenging peptides.

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Section: Purification Of 3 Novel ␦-Conotoxins From Crude Venom-mentioning

confidence: 92%

δ-Conotoxins Synthesized Using an Acid-cleavable Solubility Tag Approach Reveal Key Structural Determinants for NaV Subtype Selectivity

Peigneur

Paolini-Bertrand

Gaertner

et al. 2014

Journal of Biological Chemistry

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“…Insects express only a single Na V channel subtype, and consequently they are exquisitely sensitive to modulation of its activity. As a result, Na V channels are the most common target of chemical insecticides and they are disproportionately represented in the venoms of arthropod predators [51,53,[78][79][80]. In contrast with insects, humans express nine different Na V channel subtypes (Na V 1.1-Na V 1.9), many of which are important therapeutic targets.…”

Section: Turning Down the Gain On Pain: Selective Inhibition Of Na V mentioning

confidence: 99%

Centipede venoms as a source of drug leads

Undheim

Jenner

King

2016

Expert Opinion on Drug Discovery

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Introduction: Centipedes are one of the oldest and most successful lineages of venomous terrestrial predators. Despite their use for centuries in traditional medicine, centipede venoms remain poorly studied. However, recent work indicates that centipede venoms are highly complex chemical arsenals that are rich in disulfide-constrained peptides that have novel pharmacology and three-dimensional structure. Areas covered:This review summarizes what is currently know about centipede venom proteins, with a focus on disulfide-rich peptides that have novel or unexpected pharmacology that might be useful from a therapeutic perspective. We also highlight the remarkable diversity of constrained threedimensional peptide scaffolds present in these venoms that might be useful for bioengineering of drug leads. Expert opinion:The resurgence of interest in peptide drugs has stimulated interest in venoms as a source of highly stable, disulfide-constrained peptides with potential as therapeutics. Well-studied venomous taxa such as cone snails and snakes have yielded FDA-approved drugs, while ancient invertebrate predators such as spiders and sea anemones have yielded molecules that are currently in preclinical studies and clinical trials, respectively. However, until recently, the paucity of research on centipede venoms made it easy to discount them as a potential source of peptides with therapeutically useful properties. Seminal studies over the past five years have revealed that centipede venoms have exceedingly complex proteomes that are perhaps richer than any other venom in unique disulfide-rich peptide scaffolds. Like most arthropod predators, centipede venoms are rich in peptides that target neuronal ion channels and receptors, but it is also becoming increasingly apparent that many of these peptides have novel or unexpected pharmacological properties with potential applications in drug discovery and development.

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“…Although the immense contribution of chemical insecticides to increases in global agricultural production over the past half-century cannot be overlooked, the scope for use of chemical insecticides to control arthropod pests is declining, largely because of the cancellation or withdrawal of chemical insecticides from the market due to the development of insect resistances, environmental legislation, lack of discovery of new chemical insecticides, environmental activism, and public pressure (King and Hardy, 2013;Smith et al, 2013). Thus, a major challenge for the future is to increase crop productivity in a sustainable manner with less reliance on chemical insecticides.…”

Section: Crop Losses Due To Arthropod Pests and The Current Status Ofmentioning

confidence: 99%

“…Arthropod predators such as spiders, scorpions, and centipedes mainly use their venom to catch insect prey, and consequently their venoms contain many insecticidal peptides (Schwartz et al, 2012;King and Hardy, 2013;Smith et al, 2013). Due to hundreds of millions of years of evolutionary selection pressure, these insecticidal toxins have developed remarkable selectivity and potency for their molecular targets (Smith et al, 2013).…”

Section: Insecticidal Venom Peptides From Arthropod Predatorsmentioning

confidence: 99%

“…Due to hundreds of millions of years of evolutionary selection pressure, these insecticidal toxins have developed remarkable selectivity and potency for their molecular targets (Smith et al, 2013). In the venoms of spiders alone, which are among the world's most successful insect predators, it is estimated that millions of insecticidal toxins are yet to be discovered (Schwartz et al, 2012;King and Hardy, 2013;Smith et al, 2013).…”

Section: Insecticidal Venom Peptides From Arthropod Predatorsmentioning

confidence: 99%

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Engineering insect-resistant plants by transgenic expression of an insecticidal spider-venom peptide

Alam¹

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The insecticidal spider-venom peptide ω-hexatoxin-Hv1a (Hv1a) from the Australian Blue Mountains funnel-web spider Hadronyche versuta is one of the most potent insect-specific neurotoxins isolated to date. Hv1a blocks voltage-gated calcium channels in the insect central nervous system, a mechanism quite distinct from existing chemical insecticides. It induces a slow-onset paralysis that precedes death in a taxonomically wide range of insects. Hv1a's broad spectrum of target insects, novel mode of action, and absence of toxicity to vertebrates makes the Hv1a gene an attractive tool for generating insectresistant transgenic crops.The oral activity of Hv1a can be enhanced by coupling it to the plant lectin Galanthus nivalis agglutinin (GNA) or with the minor capsid protein of pea enation mosaic virus (CP).Recombinant fusions of Hv1a with GNA were produced using the Pichia pastoris expression system to study the intrinsic insecticidal activity of Hv1a-GNA and GNA-Hv1a fusion proteins. By using injection bioassays with houseflies, we found that the intrinsic insecticidal activity of Hv1a was maintained when it was fused to GNA. Moreover, feeding bioassays with diamondback moth larvae revealed that fusion of Hv1a to GNA, in either orientation, enhances its oral insecticidal activity.In order to generate transgenic plants expressing Hv1a alone or fused to GNA or CP, transformation vectors were constructed by ligating synthesised genes in the pAOV binary vector with the constitutive Cauliflower Mosaic Virus 35S promoter (35S) or the phloem tissue-specific Arabidopsis thaliana SUCROSE TRANSPORTER 2 (SUC2) promoter.Homozygous transgenic Arabidopsis were generated using the floral dip method of Agrobacterium-mediated plant transformation and subsequent herbicide selection. PCR of genomic DNA and western blotting were used to confirm integration of the transgenes and protein expression in the transgenic Arabidopsis respectively. Initial experiments revealed a very high level of mortality of Helicoverpa armigera larvae on wild-type plants due to the presence of endogenous glucosinolates, which masked the insecticidal effects of the transgenes Thus, a new set of transgenic plants was generated using an Arabidopsis cyp79B2 cyp79B myb28 myb29 quadruple mutant that lacks endogenous glucosinolates.Bioassays revealed that H. armigera larvae had a lower level of survival and retarded growth when fed on leaves of transgenic Arabidopsis expressing Hv1a toxins under 35S promoter control compared with those fed on gluc-null control plants. Moreover, larval mortality was higher for plants expressing Hv1a/GNA fusions than those expressing Hv1a or GNA alone. The highest larval mortality, lowest larval weight gain, and lowest level of leaf damage were observed for larvae fed on plants expressing GNA-Hv1a. Mortality was extremely high (~90%) for larvae fed on GNA-Hv1a plants for 15 days. The resistance to cotton bollworms conferred by expression of GNA-Hv1a in transgenic Arabidopsis highlights the potential of Hv1a transgenes as an ...

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The insecticidal potential of venom peptides

Cited by 99 publications

References 206 publications

δ-Conotoxins Synthesized Using an Acid-cleavable Solubility Tag Approach Reveal Key Structural Determinants for NaV Subtype Selectivity

δ-Conotoxins Synthesized Using an Acid-cleavable Solubility Tag Approach Reveal Key Structural Determinants for NaV Subtype Selectivity

Centipede venoms as a source of drug leads

Engineering insect-resistant plants by transgenic expression of an insecticidal spider-venom peptide

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