Biological control of insects

Drug – bio-affecting and body treating compositions – Enzyme or coenzyme containing – Hydrolases

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435212, 514 12, A61K 3848, A61K 3800, C12N 948

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active

059852739

DESCRIPTION:

BRIEF SUMMARY
This invention relates to a method of controlling insects and to compositions therefor.
In particular the invention relates to the control of infestations by insects of animals or plants, and to the prophylaxis of infections of animals or plants which are transmitted by insects. The invention is also applicable to the amelioration of infections which are consequential upon infestation by insects.
More particularly the invention relates to the use of compositions comprising peptidase inhibitors for the control of insects, and to the use of insect-resistant transgenic organisms which express peptidase inhibitors.


BACKGROUND OF THE INVENTION

Insects cause significant pest problems in a wide variety of animals and plants worldwide, with estimates of 13% of crop production lost each year despite current control measures. Insect species of the orders Lepidoptera, Hemiptera, Orthoptera, Coleoptera, Psocoptera, Isoptera, Thysanoptera and Homoptera cause massive losses to many horticultural and broadacre crops and stored and manufactured grain products. Diptera, Anaplura, Malophaga and Siphonaptera cause parasitic infections in animals and man. Other orders (Hymenoptera, Dictyoptera, Isoptera) include important domestic and industrial pests.
Many of the known control measures for insects depend on the use of chemical insecticides, for example chlorinated hydrocarbons (DDT, endosulfan etc), organophosphates (chlorpyrifos, diazinon, malathion, parathion), organocarbamates (carbaryl, methomyl, proxypur) and synthetic pyrethroids (cypermethrin, deltamethrin).
Problems associated with the use of chemical insecticides include the development of resistance by target insects (organophosphates, synthetic pyrethroids), the persistence of the chemicals in the environment and in plant and animal tissues, and the harmful effects on non-target organisms (organochlorines, insect growth regulators).
Boron compounds (borax, polybor) have also been used for insecticidal purposes. Boron compounds are stable, kill insects relatively slowly at practical doses (Mullens and Rodriguez, 1992), and ingestion of large doses by humans can be lethal (Anon, 1991)
Other categories of insecticide include insect growth regulators (IGRs) and insecticidal bacterial toxins (eg. Bacillus thuringiensis (Bt) toxins). IGRs are compounds that interfere in some way with chitin synthesis. They include juvenile hormone analogues (methoprene), chitin synthesis inhibitors (fenoxycarb, diflubenzuron, flurazuron) and triazine derivatives (cyromazine). Resistance has been noted to many classes of IGR. Resistance is also developing in certain lepidoterans to Bt toxins. It is technically difficult with both IGRs and Bt toxins to ensure adequate insect kill at an appropriate stage in its life cycle. Some IGRs are stable and may pose environmental hazards.
The most useful groups of insecticides are those having high insecticidal activity and low environmental persistance (organophosphates, synthetic pyrethroids). The greatest problem associated with these, however, is the development of resistance by target insects. It is believed that 90% of insecticide use is still based on classical neurotoxic insecticides. The search for alternative low-residual insecticides which are effective on insects resistant to existing insecticides is thus particularly urgent.
Agents referred to as synergists may be used to maximise effectiveness of particular insecticides. Synergists may or may not be insecticidal in their own right. Blood and Studdert (1988) define a synergist as an agent that acts with or enhances the action of another. As an example, it may be noted that piperonyl butoxide is a synergist for synthetic pyrethroids. Synergists which are effective in combination with a particular insecticide may not be effective in combination with other insecticides. Synergists can be used to overcome problems of insect resistance, although insect resistance to synergists can also occur. The role of synergists in insecticidal formulations can be vital for achieving a commercially via

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Baker, Digestive Proteinases of Sitophilus weevils (Coleoptera: Curculionidae) and Their Response to Inhibitors from Wheat and Corn Flour, Can. J. Zool. 60:3206-3214, 1982.
Ferreira and Terra, Substrate Specificity and Binding Loci for Inhibitors in an Aminopeptidas Purified from the Plasma . . . Cells of an Insect Larva, Archives of Biochemistry and Biophysics 244:478-485, 1986.
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Christeller, John T., "The Interaction of the Elastase Inhibitor, Eglin c, with Insect Digestive Endopeptidases: Effect of pH . . . ," Insect Biochem. Molec. Biol, vol. 24, No. 1, pp. 103-109 (1994).
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