WO1997007681A1 - Inhibiteurs de proteinases pepsine ou a effet pepsine utilises comme acaricides - Google Patents

Inhibiteurs de proteinases pepsine ou a effet pepsine utilises comme acaricides Download PDF

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Publication number
WO1997007681A1
WO1997007681A1 PCT/US1996/014277 US9614277W WO9707681A1 WO 1997007681 A1 WO1997007681 A1 WO 1997007681A1 US 9614277 W US9614277 W US 9614277W WO 9707681 A1 WO9707681 A1 WO 9707681A1
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WO
WIPO (PCT)
Prior art keywords
pepsin
compound
compounds
mite
mites
Prior art date
Application number
PCT/US1996/014277
Other languages
English (en)
Inventor
Ida K. Yu
Original Assignee
Nzym, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Nzym, Inc. filed Critical Nzym, Inc.
Priority to AU69672/96A priority Critical patent/AU6967296A/en
Publication of WO1997007681A1 publication Critical patent/WO1997007681A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N61/00—Biocides, pest repellants or attractants, or plant growth regulators containing substances of unknown or undetermined composition, e.g. substances characterised only by the mode of action
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/44—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a nitrogen atom attached to the same carbon skeleton by a single or double bond, this nitrogen atom not being a member of a derivative or of a thio analogue of a carboxylic group, e.g. amino-carboxylic acids
    • A01N37/46—N-acyl derivatives

Definitions

  • This invention is in the field of agricultural acaricides, more particularly, in the field of acaricide specific for Tetranychus species.
  • Mites that are known to be significant agricultural pests include those that belong to the families Tetranychidae, Tyroglyphidae, Glycyphagidae, Eriophydae, and Panonychidae. Mites belonging to the family Tetranychidae, such as Tetranychus urticae and Tetranychus cii-JiaJarinus, are of particular commercial significance. It is of particular interest to prepare compounds that have acaricidal activity so as to prevent and reduce mite infestations. It is also of interest to provide improved methods of screening for compounds that have acaricidal activity.
  • One aspect of the invention is to provide for novel methods of controlling mite infestations of plants.
  • the novel methods employ the step of applying an effective amount of a compound that can inhibit the proteolytic activity of pepsin and pepsin-like proteinase.
  • a preferred compound for use in the subject methods is pepstatin A.
  • Another aspect of the invention is to provide formulations for use in applying to plants so as to control mites.
  • the formulations comprise one or more inert carrier and a compound that can inhibit the proteolytic activity of pepsin.
  • a preferred acaricidal compound for use inclusion in the subject formulations is pepstatin A.
  • Another aspect of the invention is to provide improved methods for the screening of compounds that have acaricidal activity.
  • the screening method of the invention limits the range of compounds for screening to those compounds capable of inhibiting the proteolytic activity of pepsin and pepsin ⁇ like proteinase.
  • the invention provided herein exploits the discovery that many compounds capable of inhibiting the proteolytic activity of pepsin have acaricidal activity against mites, especially the mite Tetranychus urticae .
  • One aspect of the invention is to provide novel methods of controlling mite infestations of plants.
  • the term "controlling" as used with respect to mites refers both to the prevention of mite infestations and to the reduction of the number of mites already present on a given plant suffering from a mite infestation.
  • compounds for use in the subject methods have acaricidal activity, i.e., the compounds can kill mites in relatively low concentrations.
  • the compounds for use in the subject methods may have acaricidal activity against one or more of the three stages of the mite life cycle, i.e., the egg stage, the larval stage, and the adult stage.
  • the acaricidal compounds for use in the subject method are inhibitors of the proteolytic activity of the enzyme pepsin.
  • pepsin refers to pepsin as produced in the stomach of any of a variety of mammals.
  • the compounds for use in the methods of the invention may inhibit bovine pepsin, ovine pepsin, porcine pepsin, and pepsin-like enzymes.
  • pepsin-like enzyme refers to a proteinase that has three-dimensional structural homology to the enzyme pepsin, particularly the two aspartic acid residues present at the active site in pepsin.
  • pepsin inhibitor refers to a compounds that interacts with pepsin and can significantly lower the turnover rate of a pepsin catalyzed proteolytic reaction. Many pepsin inhibitors are known to the person of ordinary skill in the art and can be found by referring to numerous publications such as the Handbook of Enzvme Inhibitors, 2nd Edition (ISBN 156081-219- 2) , and the like.
  • pepsin inhibitors of interest are described in, among other places, US Patent 4,980,283, US Patent 4,874,745, US Patent 4,904,583, US Patent 4,874,745, US Patent 4,746,648, US Patent 4,725,580, US Patent 4,185,096, US Patent 3,975,366, US Patent 3,963,579, US Patent 3,869,347, US Patent 3,840,516, and US Patent 3,740,319. Additionally, the invention contemplates the use of pepsin inhibitors that have not yet been identified or synthesized in the methods of the invention. The three dimensional structure of pepsin has been established and the person of ordinary skill in the art may design novel compounds that act as pepsin inhibitor by use of molecular modeling computer software.
  • pepsin inhibitors may readily be evaluated for their proteolytic inhibitory properties by measuring the effect of the suspected pepsin inhibitor on a pepsin catalyzed reaction.
  • Preferred pepsin inhibitors for use in the subject methods are pepsin inhibitors that lack significant toxicity for humans and for plants to be treated by the subject methods. Not all inhibitors of pepsin proteolytic activity have acaricidal activity; however, pepsin inhibitors having acaricidal may readily be detected by screening pepsin inhibitors of interest in bioassays for toxicity to mites.
  • such assays involve directly applying pepsin inhibitors of interest to either mite adults, larvae, or eggs and measuring the survival rate, or allowing mite adults or larvae to ingest pepsin inhibitors of interest and then measuring survival rates.
  • Preferred compounds for use in the subject methods are pepstatin A and analogs thereof having anti-pepsin activity.
  • the methods of the invention may be used to control many different species of mites, the subject methods are particularly effective against Tetranychus urticae .
  • the methods of the invention comprise the step of applying a pepsin inhibitor having acaricidal activity to a plant of interest.
  • the acaricide may be applied by a variety of means such as spraying a liquid, dusting a powder and the like, well known to the person of ordinary skill in the art of crop protection.
  • the particular method of application selected will be dependent upon a number of factors such as the type of plant, the formulation selected, the arrangement of plants in the field, weather conditions, and the like.
  • the actual amount of acaracide applied to each plant may be varied so as to achieve the desired degree of pest control.
  • the optimal dosage for a specific plant, specific mite species, and specific pepsin inhibitor, under a given set of environmental conditions may be determined through routine experimentation in which the dosage is systematically varied.
  • the methods of the invention preferably use the acaricidal pepsin inhibitor in a formulation adapted for application to plants.
  • the acaricidal pepsin inhibitors for use in the subject methods will generally be used in formulation with a liquid or solid diluent or with an organic solvent.
  • the invention specifically provides for numerous formulations comprising pepsin inhibitors for use as acaricides on plants and a inert carrier, such as a diluent.
  • the term "inert" is used to indicate that the carrier does not have significant acaricidal activity.
  • the formulations of the inventions comprise an acaricidal pepsin inhibitor and a diluent or surfactant, which may not act as an inert carrier.
  • the formulations may further comprise additional compounds that have acaricidal activity.
  • Useful formulations can be prepared in conventional ways. They include dusts, granules, pellets, solutions, emulsions, wettable powders, emuisifiable concentrates and the like. Many of these may be applied directly. Sprayable formulations can be extended in suitable media and used at spray volumes of from about one to several hundred liters per hectare. High strength compositions are primarily used as intermediates for further formulation.
  • the formulations broadly, contain about 1% to 99% by weight of active ingredient(s) and at least one of a) about 0.1% to 35% surfactant(s) and b) about 5% to 99% solid or liquid inert diluent(s) . More specifically, they will contain these ingredients in the following approximate proportions:
  • Typical solid diluents are described in Watkins et al. , "Handbook of Insecticide Dust Diluents and Carriers," 2nd Ed., Dorland Books, Caldwell, N.J. The more absorptive diluents are preferred for the wettable powders and the denser ones for dusts.
  • Typical liquid diluents and solvents are described in Marsden, “Solvents Guide,” 2nd Ed., Interscience, New York, N.Y., 1950. Solubility under 0.1% is preferred for suspension concentrates; solution concentrates are preferably stable against phase separation at 0°C.
  • compositions are well known. Solutions are prepared by simply mixing the ingredients. Fine solid compositions are made by blending and, usually, grinding as in a hammer or fluid energy mill. Suspensions are prepared by wet milling (see, for example, Littler, U.S. Pat. No. 3,060,084). Granules and pellets may be made by spraying the active material upon prefoamed granular carriers or by agglomeration techniques. See J. E. Browning,
  • Another aspect of the invention is to provide novel methods of screening for compounds that have acaricidal activity, especially acaricidal activity against Tetranychus species, particularly Tetranychus urticae .
  • Conventional methods of screening compounds for acaricidal activity involve the use of relatively simple bioassays in which the toxicity of potential acaricidal is measured against mite eggs, larvae, or adults.
  • a significant disadvantage of these previous screening methods is that the range of potential compounds for screening is virtually infinite.
  • the improved methods of screening for acaricidal compounds described herein limit the potential range of compounds for screening to those compounds that are capable of inhibiting the proteolytic activity of pepsin.
  • the improved screening method of the invention comprises the steps of limiting the compounds for screening to pepsin inhibitors and then applying selected pepsin inhibitors to mites (eggs, larvae, adults) , either directly or through ingestion, and measuring the survival rate of the mites.
  • aqueous solutions were applied to eggs, larvae, and adults of the following species: Aphis craccivora, (Cowpea Aphid) ; Nilaparvata lugens, (Rice Plant Hopper) ; Tetranychus urticae , (Two Spotted Spider Mide) ; Spodoptera Littoralls , (Cotton Leafworm) ; Heliothis virescens , (Tobacco Budword) ; Anthonomus gran ⁇ is , (Cotton Boll Weevil); and Diabrotica balteata , (Banded Cucumber Beetle) .
  • Pepstatin A was effective against larvae and adults.
  • Soybean trypsin inhibitor, lima bean trypsin inhibitor, and pentamidine isothionate were effective against larvae and adults.
  • Aprotinin was effective against adults only.

Abstract

Nouveaux procédés de lutte contre l'invasion des plantes par les acariens. Les nouveaux procédés consistent à appliquer une quantité efficace d'un composé capable d'inhiber l'activité protéolytique des protéinase pepsine et similaires. Un composé préféré pour l'utilisation dans les procédés décrits est la pepstatine A. L'invention concerne en outre des préparations à appliquer aux plantes pour lutter contre les acariens. Ces préparations sont constituées d'un ou plusieurs porteurs inertes et d'un composé pouvant inhiber l'activité protéolytique de la pepsine. Un composé acaricide préféré à inclure dans les préparations décrites est la pepstatine A. L'invention concerne également des procédés améliorés de recherche de composés présentant une activité acaricide. Le procédé de tri décrit limite la gamme de composés à ceux qui sont capables d'inhiber l'activité protéolytique des protéinases pepsine et à effet pepsine.
PCT/US1996/014277 1995-08-24 1996-08-23 Inhibiteurs de proteinases pepsine ou a effet pepsine utilises comme acaricides WO1997007681A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU69672/96A AU6967296A (en) 1995-08-24 1996-08-23 Inhibitors of pepsin or pepsin-like proteinases as acaricides

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US273495P 1995-08-24 1995-08-24
US60/002,734 1995-08-24

Publications (1)

Publication Number Publication Date
WO1997007681A1 true WO1997007681A1 (fr) 1997-03-06

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AU (1) AU6967296A (fr)
WO (1) WO1997007681A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN117402221A (zh) * 2023-10-17 2024-01-16 湖北省生物农药工程研究中心 用于防治螨害的蛋白组合物及应用
CN117402221B (zh) * 2023-10-17 2024-05-10 湖北省生物农药工程研究中心 用于防治螨害的蛋白组合物及应用

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0135343A1 (fr) * 1983-08-19 1985-03-27 Agricultural Genetics Company Limited Méthode de protection des plantes
EP0348348A2 (fr) * 1988-06-20 1989-12-27 Ciba-Geigy Ag Procédé de lutte contre les parasites des plantes
WO1991009060A1 (fr) * 1989-12-11 1991-06-27 Cornell Research Foundation, Inc. Agent d'inhibition de proteinase et leur procedes d'utilisation
JPH05238913A (ja) * 1992-02-27 1993-09-17 Suntory Ltd 農園芸用殺虫剤
WO1994016565A1 (fr) * 1993-01-25 1994-08-04 Pioneer Hi-Bred International, Inc. Aprotinine et combinaisons synergetiques de ladite substance avec des lectines utilisees en tant que larvicides contre les insectes parasites des cultures agricoles, materiaux recoltes a partir desdites cultures et produits obtenus a partir desdits materiaux recoltes

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0135343A1 (fr) * 1983-08-19 1985-03-27 Agricultural Genetics Company Limited Méthode de protection des plantes
EP0348348A2 (fr) * 1988-06-20 1989-12-27 Ciba-Geigy Ag Procédé de lutte contre les parasites des plantes
WO1991009060A1 (fr) * 1989-12-11 1991-06-27 Cornell Research Foundation, Inc. Agent d'inhibition de proteinase et leur procedes d'utilisation
JPH05238913A (ja) * 1992-02-27 1993-09-17 Suntory Ltd 農園芸用殺虫剤
WO1994016565A1 (fr) * 1993-01-25 1994-08-04 Pioneer Hi-Bred International, Inc. Aprotinine et combinaisons synergetiques de ladite substance avec des lectines utilisees en tant que larvicides contre les insectes parasites des cultures agricoles, materiaux recoltes a partir desdites cultures et produits obtenus a partir desdits materiaux recoltes

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
DATABASE CROPU STN-International; D.MICHAUD ET AL.: "Pest control with proteinase inhibitors: is it compatible with IPM strategies?", XP002021775 *
DATABASE WPI Section Ch Week 9342, Derwent World Patents Index; Class C03, AN 93-331338, XP002021776 *
HORTSCIENCE, vol. 30, no. 4, 1995, pages 801 *
PATENT ABSTRACTS OF JAPAN vol. 177, no. 04 (C - 1146) 22 December 1993 (1993-12-22) *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN117402221A (zh) * 2023-10-17 2024-01-16 湖北省生物农药工程研究中心 用于防治螨害的蛋白组合物及应用
CN117402221B (zh) * 2023-10-17 2024-05-10 湖北省生物农药工程研究中心 用于防治螨害的蛋白组合物及应用

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