Insect neuropeptides 2

Abstract

To provide insect neuropeptides 2.SOLUTION: The present invention relates to natural or natural-like analogues of insect pyrokinin neuropeptide [Pyr]-AIMARPQVPRL-[NH2] (SEQ ID NO: 2) having activity against insects, e.g., hemipteran, dipteran, lepidopteran, blattodean and / or coleopteran insects, such as aphids and fruit flies, and to their use as insect control agents (e.g., insecticides) and plant protection agents.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to natural or natural-like analogues of insect pyrokinin neuropeptides having activity against insects, such as Hemiptera, Diptera, Lepidoptera, Blattophila and / or Coleoptera insects, such as aphids, moths and fruit flies, and their use as insect control agents (e.g. insecticides) and plant protection agents. [Background technology]

[0002] With the worldwide reliance on broad-spectrum pesticides, whose damaging effects are well documented, there is an increasing need to develop more environmentally friendly target-specific pesticides that protect valuable crop plants. The development and use of neuropeptides, and their synthetic analogues, offers a promising avenue for more environmentally friendly target-specific pesticidal agents.

[0003] In insects, neuropeptides are regulatory peptides with functional roles in growth and development, behavior and reproduction, metabolism and homeostasis, and muscle movement. The insect neuropeptide family is large and includes insect kinin and CAPA (CAPA, CAP2b, CAPA3) neuropeptides, AKH peptides, and pyrokinin peptides.

[0004] Due to their high specificity, insect neuropeptides and their cognate receptors (G protein-coupled receptors, GPCRs) can be developed into insecticidal agents that selectively reduce the fitness of target pest insects while minimizing adverse environmental effects and minimizing harm to other non-target species, such as pollinators whose populations have been dangerously reduced by the use of pesticides / insecticides.

[0005] There have been attempts in the art to provide modified synthetic analogs of such insect neuropeptides for use as targeted insecticides that have shown promising results, but while these modified peptides are desirable and effective, they can be challenging to market in many areas where the use of such modified peptides is tightly regulated. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] International Publication No. 2020 / 021041 Brochure [Patent Document 2] International Publication No. 2023 / 161802 Brochure [Patent Document 3] International Publication No. 2022 / 264053 Brochure [Patent Document 4] International Publication No. 2022 / 189386 Brochure [Patent Document 5] International Publication No. 2022 / 165248 Brochure [Patent Document 6] International Publication No. 2021 / 152093 Brochure [Patent Document 7] International Publication No. 2020 / 212612 Brochure [Patent Document 8] International Publication No. 2020 / 021041 Brochure [Non-patent literature]

[0007] [Non-Patent Document 1] classification Systema Naturae,Brands,SJ(comp.)1989-2005.Systema Naturae 2000.Amsterdam,The Netherlands,[http: / / sn2000.taxonomy.nl / ] [Non-Patent Document 2] Developing the Arsenal Against Pest and Vector Dipterans:Inputs of Transgenic and Paratransgenic Biotechnologies,Ogaugwu and Durvasula,IntechOpen,2017:DOI:10.5772 / 66440 [Non-Patent Document 3] Mulqueen, 2003 [Non-Patent Document 4] Mozafari, MR “Nanoliposomes:preparation and analysis.”Liposomes:Methods and Protocols,Volume 1:Pharmaceutical Nanocarriers(2010):29-50 Summary of the Invention [Problem to be solved by the invention]

[0008] The present invention aims to solve one or more of the above problems and provides novel naturally occurring pyrokinin neuropeptides, and naturally occurring-like variants or analogues thereof, for use as insect control agents and plant protection agents. [Means for solving the problem]

[0009] The present inventors have discovered novel pyrokinin peptides, and naturally occurring variants or analogs thereof, which have insecticidal activity against insects, e.g., Hemiptera, Diptera, Lepidoptera, Blattophila and / or Coleoptera insects, while having little or no effect against important pollinator species, e.g., honeybees, and therefore are of potential use as pest control agents or insecticides.

[0010] Thus, in a first aspect, the present invention provides a compound of formula (I): R 1 -Y 1 -ZY 2 -R 2 (I) or a salt or solvate thereof, During the ceremony: R 1 is hydrogen (which can be represented as "H-" or "Hy-"); 1~4 alkyl (e.g., methyl, ethyl, propyl, butyl), formyl, acyl, fatty acyl, sugar moiety, phosphate or sulfate, or R 1 is the formula [ka] is a pyroglutamate group of Alkyl, formyl, acyl or fatty acyl is oxo or C 1~6 may be optionally substituted with one or more groups selected from an alkyl or sugar moiety, phosphate or sulfate; Y 1 is absent or a peptide containing 1-2 amino acids; Z is the formula AIMARPQVPRL (SEQ ID NO: 1) is a peptide according to Y 2 is absent or a peptide containing 1-2 amino acids; R 2 , NH2, NR 2a H, N.R. 2a R 2b , OH or OR 2a where R 2a and R 2b Each of, if present, independently, C 1~6 - alkyl (for example methyl, ethyl, propyl, butyl, pentyl or hexyl).

[0011] In another aspect, there is provided a composition comprising a compound as defined herein, or a salt thereof, mixed with one or more solvents, carriers, excipients, adjuvants, preservatives, dispersants, emulsifiers, or synergists.Suitably, the composition is an agricultural composition, an insect control composition, or a plant protection composition.

[0012] In another aspect, there is provided the use of the compound defined herein, or its salt, or the composition defined herein, as an insect control agent.It can be used as an insecticide against insects that code for pyrokinin peptides.It can be used as an insecticide against Hemiptera, Diptera, Lepidoptera, Blattodea and / or Coleoptera insects, preferably Hemiptera, Diptera and / or Lepidoptera insects, most preferably Hemiptera insects, such as aphids.

[0013] In another aspect, there is provided a method for increasing insect mortality, comprising contacting an insect population with a compound as defined herein, or a salt thereof, or a composition as defined herein. Suitably, the insect is an insect encoding a pyrokinin peptide, such as a Hemipteran, Diptera, Lepidoptera, Blattophila and / or Coleoptera insect, preferably a Hemipteran, Diptera and / or Lepidoptera insect, most preferably a Hemipteran insect, such as an aphid.

[0014] In another aspect, there is provided a method of increasing mortality in Hemiptera, Diptera, Lepidoptera, Blattodea and / or Coleoptera insects, the method comprising contacting a population of Hemiptera, Diptera, Lepidoptera, Blattodea and / or Coleoptera insects with a compound as defined herein, or a salt thereof, or a composition as defined herein. Preferably, the insects are Hemiptera insects, such as aphids.

[0015] In another aspect, there is provided the use of a compound as defined herein, or a salt thereof, or a composition as defined herein, as a plant protection agent for protecting plants against insects encoding pyrokinin peptides, preferably the insects being hemipteran insects, such as aphids.

[0016] In another aspect, there is provided the use of a compound as defined herein, or a salt thereof, or a composition as defined herein, as a plant protection agent for protecting plants against Hemipteran, Dipteran, Lepidopteran, Blattophilan and / or Coleopteran insects, preferably Hemipteran, Dipteran and / or Lepidopteran insects, most preferably Lepidopteran insects, such as moths.

[0017] In another aspect, there is provided a method for inhibiting infestation of a plant by insects encoding pyrokinin peptides, the method comprising contacting the plant with a compound as defined herein, or a salt thereof, or a composition as defined herein. Suitably, the compound or composition is applied to the plant while the plant is free or substantially free of insects encoding pyrokinin peptides.

[0018] In another aspect, there is provided a method for inhibiting infestation of a plant by Hemiptera, Diptera, Coleoptera, Blattodea and / or Lepidoptera insects, comprising contacting the plant with a compound as defined herein, or a salt thereof, or a composition as defined herein. Suitably, the compound or composition is applied to the plant while the plant is free or substantially free of Hemiptera, Diptera, Lepidoptera, Blattodea and / or Coleoptera insects. Preferably, the insects are selected from Hemiptera, Diptera and / or Lepidoptera insects, most preferably Hemiptera insects, such as aphids.

[0019] In another aspect, there is provided a method for reducing infestation of a plant by insects encoding pyrokinin peptides or reducing the load of insects encoding pyrokinin peptides on a plant, the method comprising contacting the plant with a compound as defined herein, or a salt thereof, or a composition as defined herein.

[0020] In another aspect, there is provided a method for reducing the infestation of plants with Hemiptera, Diptera, Lepidoptera, Blattodea and / or Coleoptera insects or reducing the load of Hemiptera, Diptera, Lepidoptera, Blattodea and / or Coleoptera insects on plants, comprising contacting the plant with a compound as defined herein, or a salt thereof, or a composition as defined herein.Preferably, the insects are selected from Hemiptera, Diptera and / or Lepidoptera insects, most preferably Hemiptera insects, such as aphids.In one embodiment, the compounds, compositions and agents of the present invention are suitably active against the aphid species Myzus persicae.

[0021] Suitable insects encoding pyrokinin peptides include Hemiptera, Diptera, Lepidoptera, Blattodea and / or Coleoptera insects, preferably Hemiptera, Diptera and / or Lepidoptera insects. In a preferred embodiment, the insect encoding pyrokinin peptides is a Hemiptera insect, such as an aphid.

[0022] In another aspect, there is provided a method of producing an insecticidal compound according to the first aspect, the method comprising: (a) chemically synthesizing an insecticidal compound of formula (I) or a precursor thereof; Includes.

[0023] In one embodiment, the chemical synthesis includes the methods described in the Examples. In one embodiment, the chemical synthesis includes the methods and steps shown in FIG.

[0024] Further features of aspects and embodiments of the invention are now defined in the following heading sections. Any feature in any section may be combined with any aspect of the embodiments in any workable combination. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0025] definition Throughout this specification and claims, the conventional three letter and one letter codes for the naturally occurring amino acids are used: A (Ala), G (Gly), L (Leu), I (Ile), V (Val), F (Phe), W (Trp), S (Ser), T (Thr), Y (Tyr), N (Asn), Q (Gln), D (Asp), E (Glu), K (Lys), R (Arg), H (His), M (Met), C (Cys) and P (Pro).

[0026] "Amino acid," as referred to herein, may refer to naturally occurring amino acids or any other amino acid, including synthetic and non-proteinogenic amino acids. "Naturally occurring" refers in this context to the 20 amino acids encoded by the standard genetic code, which are sometimes referred to as proteinogenic amino acids.

[0027] The term amino acid is an abbreviation for α-amino [alpha-amino] carboxylic acid. Each molecule contains a central carbon atom, called the α-carbon, to which both the amino and carboxyl groups are attached. The remaining two bonds of the α-carbon atom are generally filled by a hydrogen (H) atom and a side chain, below designated as R. [ka]

[0028] Unless otherwise specified, amino acid residues in the peptides of the present invention are of the L-configuration. As used herein, the terms "polypeptide", "protein", and "peptide" are used interchangeably and refer to polymeric forms of amino acids of any length that may include coded and non-coded amino acids. As used herein, amino acid residues are indicated above by their full names or by the standard three-letter or one-letter amino acid codes.

[0029] Notation C x~xxrefers to the number of carbon atoms in the functional group. The number in the "x" position represents the smallest number of carbon atoms, and the number in the "xx" position represents the largest number of carbon atoms. For example, C 1~6 -Alkyl refers to an alkyl group, as defined herein, having 1 to 6 carbon atoms.

[0030] The notations I, n, or t are used herein in a conventional manner with respect to various alkyl groups. Specifically, the suffixes refer to the atomic arrangement and represent straight chain ("n") or branched ("i" or "t") alkyl groups.

[0031] The term "alkyl" as used herein refers to a saturated straight or branched chain monovalent hydrocarbon group, where the alkyl group may be optionally substituted. The number of carbon atoms in an alkyl group may be specified using the notation above, for example, the term "C 1~8 Examples of alkyl groups include methyl (Me, -CH3), ethyl (Et, -CH2CH3), 1-propyl (n-Pr, n-propyl, -CH2CH2CH3), 2-propyl (i-Pr, i-propyl, -CH(CH3)2), and 1-butyl (n-Bu, n-butyl, -CH2CH2CH2CH3).

[0032] An "alkylene," "alkenylene," or "alkynylene" group is an alkyl, alkenyl, or alkynyl group that is positioned between and serves to link two other chemical groups. Thus, "C 1~6 "Alkylene" means a linear saturated divalent hydrocarbon radical of 1 to 6 carbon atoms or a branched saturated divalent hydrocarbon radical of 3 to 6 carbon atoms. Examples of alkylene radicals include methylene (-CH2-), 1,1-ethylene (-CH(CH3)-), 1,2-ethylene (-CH2CH2-), 1,1-propylene (-CH(CH2CH3)-), and 2,2-propylene (-C(CH3)2-).

[0033] The term "alkenyl," as used herein, refers to a straight or branched chain monovalent hydrocarbon group having at least one site of unsaturation, i.e., a carbon-carbon double bond. Alkenyl groups may be optionally substituted and include groups having "cis" and "trans" orientations, or alternatively, "E" and "Z" orientations. The number of carbon atoms in an alkenyl group may be specified using the notation above, for example, the term "C" is used when there are 2 to 8 carbon atoms. 2~8 Examples of alkenyl groups include, but are not limited to, ethenyl (-CH=CH2), and prop-1-enyl (-CH=CHCH3).

[0034] In the chemical structures depicted herein: [ka] The presence of represents an attachment point or group, such as those groups discussed with respect to the various functional groups.

[0035] The term "comprising" is used in the present description and claims and does not exclude other elements or steps. Where an indefinite or definite article is used when referring to a singular noun, e.g. "a" or "an", "the", this includes a plural of that noun, unless something else is specifically stated.

[0036] The term "about," as used herein, when referring to a measurable value, e.g., a parameter, amount, duration, etc., is meant to encompass variations of + / - 10% or less, preferably + / - 5% or less, more preferably + / - 1% or less, and even more preferably + / - 0.1% or less from the particular value, insofar as such variations are appropriate for practicing the disclosed invention. It should be understood that the value to which the modifier "about" refers is itself also specifically and preferably disclosed.

[0037] "Plant" as used herein means whole plants or parts thereof, including fresh fruits, vegetables, and seeds. A plant or plant part may be a living plant or part thereof. The term "plant" as used herein also encompasses ancestors and descendants of plants and plant parts, including whole plants, seeds, shoots, stems, leaves, roots (including tubers), flowers, and tissues and organs, each of the above comprising the gene / nucleic acid of interest. The term "plant" also encompasses plant cells, suspension cultures, callus tissue, embryos, meristematic regions, gametophytes, sporophytes, pollen, and microspores, again each of the above comprising the gene / nucleic acid of interest.

[0038] "Crop" as used herein means a plant species or variety that is grown to be harvested for food, livestock feed, fuel source, or any other economic purpose. As non-limiting examples, the crops include corn, cereals such as wheat, rye, barley and oats, sorghum, rice, sugar beet and fodder beet, fruits such as pome fruits (e.g., apple and pear), citrus fruits (e.g., orange, lemon, lime, grapefruit, or mandarin), stone fruits (e.g., peaches, nectarines, or plums), nuts (e.g., almonds or walnuts), soft fruits (e.g., cherries, strawberries, blackberries, or raspberries), plantain or grape vines, legume crops such as beans, lentils, peas, and soybeans, oil crops such as sunflowers, safflowers, rapeseed, canola, and other crops. The crop may be, for example, an oil plant, such as corn, castor or olive, a gourd, for example, a cucumber, a melon or a pumpkin, a fiber plant, for example, cotton, flax or hemp, a fuel crop, for example, sugarcane, kaya or switchgrass, a vegetable, for example, potato, tomato, pepper, lettuce, spinach, onion, carrot, eggplant, asparagus or cabbage, an ornamental plant, for example, a flower (for example, petunia, pelargonium, rose, tulip, lily or chrysanthemum), a shrub, a broadleaf tree (for example, poplar or willow) and an evergreen tree (for example, conifer), a grass, for example, a lawn, turf or fodder grass or other useful plants, for example, a coffee, tea, tobacco, hops, pepper, rubber or latex plant.

[0039] A "pest", as used herein, is an organism that is harmful to plants, animals, humans or human related organisms, including, but not limited to, crop pests, such as insects (defined below), household pests or insects, such as cockroaches, ants, etc., and disease vectors, such as the malaria mosquito.

[0040] "Pest infestation" or "pest disease" as used herein refers to an inflammatory condition, disease or disorder in a living organism, such as a plant, animal or human, caused by a pest.

[0041] "Active substance", "active ingredient" or "active principle", as used interchangeably herein, means biological, biochemical or chemical entities, including microorganisms, and derivatives, fragments or compounds based thereon, that have a general or specific action against harmful organisms on a target, and in particular against pests of plants, plant parts or plant products (as they occur naturally or by production, including impurities inevitably resulting from the manufacturing process).

[0042] The terms "effective amount" and "effective dose" as used herein mean the amount needed to achieve a desired result.

[0043] "Insects", as used herein, are used in a broad general sense and include all species of the superphylum Panarthropoda, including the phyla Arthropoda, Tardigrada and Onychophora (Eds., 1999, 14:131-135); this includes, but is not limited to, all the different phases of the life cycle, such as egg, larva, nymph, pupa and adult. Suitable pests are defined elsewhere herein.

[0044] "Insecticidal compound", as used herein, refers to a compound having biological activity against insects (as defined above), including, but not limited to, compounds capable of killing insects, larvicides, insect growth regulators, behavior-modifying compounds, attractants, repellents, pheromones, kairomones, allomones, and insect pathogenic fungi, viruses, and proteins. Insecticidal agents exert their biological activity preferably by contact of the compound with the insect, without the need for ingestion by the insect. This includes not only compounds or compound formulations ready for use, but also precursors in inactive form that may be activated by external factors. Possibly, the insecticide may be combined with materials to be used in combination, such as synergists or safeners, flavor or fragrance compositions. Preferably, the compound is included in a carrier, as defined above. "Included in a carrier", as used herein, means bound to or contained on the carrier by means such as, but not limited to, embedding, encapsulation, and adsorption.

[0045] Throughout this specification, including the claims which follow, unless the context requires otherwise, the words "comprise" and "including," as well as variations such as "include," "including," and "including," are understood to mean the inclusion of a stated integer or step, or group of integers or steps, but not the exclusion of any other integer or step, or group of integers or steps.

[0046] It should be noted that, as used in the specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Ranges may be expressed herein as from "about" one particular value and / or to "about" another particular value. When such a range is expressed, another embodiment includes from the one particular value and / or to the other particular value. Similarly, when values ​​are expressed as approximations, by use of the antecedent "about," it will be understood that the particular value forms another embodiment. The term "about" in reference to a numerical value is optional and may mean, for example, + / - 10%.

[0047] Compounds of the Invention Specific compounds of the invention include, for example, compounds of formula (I), where, unless otherwise stated, R 1 , Y 1 , Y 2 , R 2 Each of and any associated substituents has any of the meanings defined herein above or herein below in any of paragraphs (1) to (12): (1)R 1 is selected from hydrogen, acyl or fatty acyl, or phosphate or sulfate, or R 1 is the formula [ka] is a pyroglutamate group; wherein the acyl or fatty acyl is optionally substituted with a sugar moiety, phosphate or sulfate. (2)R 1is selected from hydrogen, formyl, acetyl (Ac), propanoyl, butanoyl, palmitoyl [palm], butyryl, cerotoyl, decanoyl, docosenoyl, dodecanoyl, eleostearoyl, heptanoyl, hexanoyl, icosanoyl, icosenoyl, lignoceroyl, linoleoyl, lipoyl, myristoleoyl, nonanoyl, octadecanoyl, octanoyl, palmitoleoyl, stearoyl, undecanoyl, and valeryl. (3)R 1 is selected from hydrogen, acetyl or palmitoyl, or R 1 is the formula [ka] is a pyroglutamate group. (4)R 1 is selected from hydrogen or palmitoyl. (5)R 1 is hydrogen. (6)R 1 is the formula [ka] is a pyroglutamate group. (7) Y 1 is a peptide that contains none, one or two amino acid residues. (8) Y 1 does not exist. (9) Y 2 is a peptide that contains none, one or two amino acid residues. (10) Y 2 does not exist. (11)R 2 , NH2, NR 2a H, N.R. 2a R 2b or OH, where R 2a and R 2b Each of, if present, independently, C 1~6 - alkyl (for example methyl, ethyl, propyl, butyl, pentyl or hexyl). (12)R2 is NH2.

[0048] Appropriately, R 1 is as defined in any one of paragraphs (1) to (6) above. More appropriately, R 1 is as defined in any one of paragraphs (3) to (6) above. Most suitably, R 1 is as defined in paragraph (4), (5) or (6) above.

[0049] Appropriately, Y 1 Or Y 2 is as defined in any one of paragraphs (7) to (10) above. Most suitably, Y 1 Or Y 2 is as defined in paragraph (8) or (10) above.

[0050] Appropriately, R 2 is as defined in paragraph (11) or (12) above. Most appropriately, R 2 is as defined in paragraph (12) above.

[0051] In a preferred embodiment, R 1 is pyroglutamate, and Y 1 and Y 2 does not exist, R 2 is NH2.

[0052] In a preferred embodiment, R 1 is pyroglutamate, and Y 2 does not exist, and Y 1 is one or two amino acids, R 2 is NH2.

[0053] In a preferred embodiment, R 1 is pyroglutamate, and Y 1 does not exist, and Y 2 is one or two amino acids, R 2is NH2.

[0054] Further description of the compounds of the present invention R 1 and R 2 The terminal groups present at the N-terminus and C-terminus of the peptide backbone are R 1 and R 2 Thus, R 1 is Y 1 It is bound to the nitrogen atom of the N-terminal amino group of R 2 is Y 2 It is bound to the C-terminal carbonyl carbon atom of

[0055] The compounds of the invention may suitably contain further functional groups at the N- or C-terminus. Suitably, the compounds may be functionalized to increase cuticular permeability or to increase stability. Suitably, the compounds may be functionalized with aromatic, aliphatic or lipophilic groups. Suitably, therefore, R 1 can be an aromatic, heteroaromatic, aliphatic or lipophilic group.

[0056] In certain embodiments, the compound may be functionalized with a lipophilic group, for example, a fatty acyl group. The fatty acyl group includes, but is not limited to, palmitoyl, butyryl, cerotoyl, decanoyl, docosenoyl, dodecanoyl, eleostearoyl, heptanoyl, hexanoyl, icosanoyl, icosenoyl, lignoceroyl, linoleoyl, lipoyl, myristoleoyl, nonanoyl, octadecanoyl, octanoyl, palmitoleoyl, stearoyl, undecanoyl, and valeryl. Suitably, therefore, R 1 The radical is palmitoyl ([Palm]), i.e.: [ka] It could be.

[0057] In one embodiment, the compound may be functionalized with an acyl group. An "acyl" group has the formula R 3a is a radical of a -C(O)- group, where R3a is C 1~6 alkyl, for example, formyl, acetyl (Ac), propanoyl, butanoyl, or R 3a is benzoyl. Suitably, R 3a The group is R 1b -C(O)-, for example, acetyl (Ac), i.e.: [ka] It could be.

[0058] In certain embodiments, R 1 The group may be substituted on the sugar moiety.

[0059] In certain embodiments, one or more amino acid residues in peptides Y and Z may be naturally modified with a sugar moiety, i.e., the amino acid residue may be a "glycosylated analog." For example, the sugar may be part of a Ser or Thr side chain modification (glycosylation), or a Lys or Arg side chain modification (glycosylation).

[0060] The sugar moiety discussed herein may be a monosaccharide or a disaccharide. Examples of monosaccharides include glucose, 6-deoxyglucose, mannose, galactose, glucosamine, galactosamine, N-acetylglucosamine, N-acetylgalactosamine, glucuronic acid, allose, altrose, gulose, idose, fucose, talose, ribose, deoxyribose, arabinose, xylose, lyxose, ribulose, xylulose, fructose, psicose, sorbose, or tagatose. Examples of disaccharides include sucrose, lactose, lactulose, allolactose, maltose, isomaltose, isomaltulose, trehalose, cellobiose, kojibiose, nigerose, sophorose, laminaribiose, gentiobiose, thiomaltose, mannobiose, or their N-, C-, or S-interglycosidic derivatives. Most suitably, the sugar moiety is selected from glucosamine or galactosamine. The sugar may be present as an N-terminal modification or as part of a Ser side chain modification. In certain embodiments, R 1 The groups may be substituted with phosphate or sulfate.

[0061] In certain embodiments, one or more amino acid residues in peptides Y and Z may be naturally modified with phosphate or sulfate. For example, the phosphate or sulfate may be part of a side chain modification, i.e., the amino acid may be phosphorylated or sulfated.

[0062] R 1 is hydrogen (which may not be noted in a particular peptide sequence, or may alternatively be indicated as "H-" or "Hy-"); 1~4 Alkyl (e.g., methyl, ethyl, propyl, butyl), -N(R 1a )-C(=N + (R 1b )(R 1c ))NR 1d R 1e , or -C(=N + (R 1b )(R 1c ))NR 1d R1e where R 1a , R 1b , R 1c , R 1d and R 1e Each of 1~4 Alkyl (eg, methyl, ethyl, propyl, butyl), preferably independently selected from hydrogen or methyl.

[0063] In some embodiments, R 1 -C(=N + (R 1b )(R 1c ))NR 1d R 1e If;R 1a , R 1b , R 1c , R 1d and R 1e is methyl, i.e., R 1 is -C(=N + Me2)NMe2.

[0064] R 1 = "H" (or "Hy"), this typically indicates a free primary amino group at the N-terminus. The other hydrogen atom of the N-terminal amino group is typically 1 The exception is when the residue at the N-terminus is N-methylated, even though the N-terminal residue has a secondary amine group. 1 can be represented as H. Thus, an N-methylated leucine residue at the N-terminus can be represented as R 1 -[n-me-L]-(wherein, R 1 However, this can be shown simply as R 1 -L-(wherein, R 1 is methyl), with no other hydrogen atoms shown.

[0065] In some embodiments, an N-terminal glutamine (Gln or Q) or N-terminal glutamic acid (Glu or E) residue can undergo conversion to form a pyroglutamate end group, [pyr]. [ka] N-terminal glutamine (Q) or glutamic acid (E) residues can undergo such conversion in biological systems by reaction with specific enzymes. The conversion can also be accomplished synthetically.

[0066] Y 1 The peptide (if present) or Z peptide therefore also contains the N-terminal [pyr] group. [ka] The N-terminal [pyr] group may be formed as a result of cyclization of an N-terminal glutamine (Gln or Q) or N-terminal glutamic acid (Glu or E) residue to form a pyroglutamate end group. Because this conversion can occur under certain biological circumstances, it is considered to be a naturally occurring modification of an N-terminal glutamine (Gln or Q) or N-terminal glutamic acid (Glu or E) residue.

[0067] Appropriately, R 2 , NH2, NR 2a H, N.R. 2a R 2b OR 2a where R 2a and R 2b Each of R is as defined herein. 2 is NH2.

[0068] Particular examples of pyrokinin peptides according to the invention include the following, or a salt or solvate thereof:

[0069] [Table 1]

[0070] In some embodiments, the compounds of the invention may be in the form of a salt or a solvate (eg, a hydrate).

[0071] The compounds of the present invention may be provided in combination with one or more additional active pesticides, such as those described herein.

[0072] Y 1 and Y 2 The peptide may contain one or two further peptide groups located between the terminal R1 and R2 groups at the N- and C-termini, respectively. Suitably, these groups are 1 and Y 2 When present, these groups are located on either side of the Z peptide group.

[0073] In one embodiment, Y 1 and Y 2 The group does not exist.

[0074] In one embodiment, the compound is Y 1 In one embodiment, the compound contains only the Y 2 Contains only the group.

[0075] In one embodiment, the compound is Y 1 and Y 2 Contains a group.

[0076] Suitably, the Y group, when present, comprises 1 or 2 amino acids. Suitably, the Y group may comprise an amino acid selected from M, R, G and K.

[0077] In one embodiment, the Y group is selected from GR, RG, KR, RK, K, R, M, and G. In one embodiment, the Y group is selected from RG, KR, and K.

[0078] In one embodiment, the compound is Y 2 contains only the group Y 2 The groups are selected from RG, KR, and K.

[0079] Modified Amino Acids or Non-Natural Amino Acid Analogues In a preferred embodiment, the pesticidal compound does not include modified amino acids or unnatural amino acid analogs.

[0080] Particularly preferred is peptide Y 1 is free of modified amino acids or unnatural amino acid analogues, when present, and 2 When present, peptide Y does not include modified amino acids or non-natural amino acid analogues. Thus, in certain embodiments, peptide Y 1 and Y 2 comprises only unmodified amino acid residues, suitably only naturally occurring amino acid residues.

[0081] In particular, peptide Z does not comprise modified amino acids or non-natural amino acid analogues.Thus, in certain embodiments, peptide Z comprises only unmodified amino acid residues, suitably only natural amino acid residues.

[0082] Activity Suitably the compounds of the invention have activity against insects. Suitably the activity is against Hemipteran, Dipteran, Lepidopteran, Blattophilan and / or Coleopteran insects.

[0083] In a preferred embodiment, the compounds of the present invention have activity against hemipteran insects.Therefore, the compounds of the present invention find particular use against hemipteran insects and may find particular use in the related uses and methods described herein.A particularly preferred hemipteran insect is aphid.

[0084] The compounds of the invention typically increase insect mortality, for example, when topically contacted with or ingested by a suitable insect. Thus, the compounds of the invention described herein (and compositions containing them) may be considered as insecticides and may be referred to as "insect control agents."

[0085] Suitably therefore, the compounds of the invention prevent insect infestation of plants and indirectly increase plant health, including increasing plant growth, yield etc. by reducing the insect load on the plant. As such, the compounds of the invention described herein (and compositions containing them) may also be considered "plant protection agents".

[0086] Without being bound by theory, any or all of the described effects may be mediated by agonistic activity at the pyrokinin receptor of the target insect. The pyrokinin receptors believed to exist in the target insect include pyrokinin receptor 1 and pyrokinin receptor 2, PK1-R and PK2-R, which are GPCRs. Suitably, the compound of the present invention binds to one or more pyrokinin receptors of the target insect. Suitably, the compound of the present invention has agonistic activity when it binds to the pyrokinin receptor of the target insect. Suitably, the compound of the present invention binds to pyrokinin receptor 1 and / or pyrokinin receptor 2. Suitably, the compound of the present invention is an agonist of pyrokinin receptor 1 and / or pyrokinin receptor 2.

[0087] Insect Control Agents The term "insect control agent" refers to an agent that is used to increase the mortality of insects (i.e., as an insecticide). The compound of the present invention or its composition may be considered as an insect control agent and may be used as an insect control agent. Suitably, therefore, the present invention provides the use of the compound of the present invention or composition as an insect control agent for, for example, Diptera insects, Hemiptera insects, Coleoptera insects, Blattodea insects, and / or Lepidoptera insects. Thus, the insect control agent may be administered to increase the mortality of a given insect or insect population.

[0088] Increased mortality, as used herein, is intended to refer to an increase in the percentage of dead insects compared to the percentage of dead insects in an otherwise identical insect population that has not been exposed to the insect control agents of the present invention.

[0089] Suitably, insect mortality can be calculated as the number of dead insects per treated area / total number of insects.Suitably, the treated area can be a plate well, or one or more leaves, or the whole plant.Suitably, insect mortality can be measured by carrying out a leaf immersion assay as described herein in the examples.

[0090] Insect control agents may be used to reduce the size of an insect population (e.g., compared to an otherwise identical insect population not exposed to the agent), or to inhibit the growth of an insect population, or to inhibit the feeding of an insect population.

[0091] An insect control composition is a composition which contains an insect control agent, ie, a compound of the present invention as described.

[0092] Plant protection agents The term "plant protection agent" refers to an agent used to protect plants or plant parts against insects, for example, against infesting or colonizing, or against being used as a food source by such insects (for example, by excreting sap). The compounds of the present invention or compositions thereof may be considered as plant protection agents and may be used as plant protection agents. Suitably, therefore, the present invention provides the use of the compounds or compositions of the present invention as plant protection agents, for example, to protect plants against Diptera insects, Hemiptera insects, Coleoptera insects, Blattodea insects, and / or Lepidoptera insects.

[0093] The infestation or colonization may be by larvae (or nymphs), adult insects, or by use as a host or reservoir for eggs, however, the terms "infestation" and "colonization" should not be construed as requiring that the presence of the insects is harmful to the plant.

[0094] The plant protection agent may be applied, inter alia, to reduce the insect load on a plant or plant part, to inhibit or reduce the infestation of the plant by insects, to inhibit (e.g., reduce the rate of) the increase in the insect load on a plant or plant part, or to maintain the plant free of insects, compared to an otherwise identical plant with an insect population not exposed to the agent. Thus, the plant protection agent may be applied to a plant or plant part that already has Hemiptera, Diptera, Coleoptera, Blattidae and / or Lepidoptera insects, or to a plant or plant part that is free or substantially free of Hemiptera, Diptera, Coleoptera, Blattidae and / or Lepidoptera insects.

[0095] A plant protection composition is a composition which comprises a plant protection agent, ie the compound of the invention as described.

[0096] plant As referred to herein, a "plant or part of a plant" or "plant or part thereof" means any part of a plant, including, but not limited to, leaves, stems, roots, flowers, sprouts, bulbs, and seeds.

[0097] Suitable plants or parts thereof which may be protected by the compounds of the present invention or compositions thereof or by the agents of the present invention include crops and plants of agricultural, horticultural or economic importance. Suitable plants may include any of the following or parts thereof: hemp (Musa textilis), alfalfa (Medicago sativa), almond oil (Prunus dulcis), anise (Pimpinella anisum), crab apple (Malus sylvestris), apricot (Prunus armeniaca), betel nut (Areca catechu), arracacia (Arracacia xanthorrhiza), arrowroot (Maranta arundinacea), artichoke (Cynara scolymus), Jerusalem artichoke (Helianthus tuberosus), asparagus (Asparagus officinalis), avocado (Persea americana), pearl millet (Pennisetum americanum), bambara groundnut (Vigna subterranean), banana (Musa paradisiaca), barley (Hordeum vulgare), and the like. vulgare, common bean (Phaseolus vulgaris), common bean (Phaseolus vigna), sugar beet (Beta vulgaris), bergamot (Citrus bergamia), rubus spp., pepper (Piper nigrum), black wattle (Acacia mearnsii), vaccinium spp., Brazil nut (Bertholletia excelsa), breadfruit (Artocarpus altilis), broad bean (Vicia faba), cauliflower (Brassica oleracea botrytis), sorghum (Sorghum bicolor), Brussels sprouts (Brassica oleracea gemmifera), buckwheat (Fagopyrum esculentum), cabbage (Brassica oleracea capitata, Brassica rapa, Brassica spp.), cacao (Theobroma cacao), melon (Cucumis melo), caraway (Carum carvi), cardamomum (Elettaria cardamomum), cardoon (Cynara cardunculus), carob (Ceratonia siliqua), wild carrot (Daucus carota), cashew (Anacardium occidentale), cassava (Manihot esculenta), castor bean (Ricinus communis), cauliflower (Brassica oleracea botrytis), celery (Apium graveolens), chayote (Sechium edule), cherry (Prunus spp.), chestnut (Castanea sativa), chickpea (Cicer arietinum), chicory (Cichorium intybus), chicory (Cichorium intybus, Capsicum spp., Cinnamomum verum, Cymbopogon nardus, Citron (Citrus medica), Mandarin orange (Citrus reticulata), Trifolium spp., Clove (Syzygium aromaticum), Cocos nucifera, Colocasia spp.; Xanthosoma spp., Coffee spp., Cola spp., Brassica napus, Maize (Zea mays), Salicaria locusta, Gossypium spp. spp.), cowpea (Vigna unguiculata), vaccinium spp., garden cress (Lepidium sativum), cucumber (Cucumis sativus), gooseberry spp.), Annona reticulata, taro (Colocasia esculenta), date palm (Phoenix dactylifera), Moringa oleifera, Phaseolus spp., garlic (Allium sativum), onion (Allium cepa), pea (Pisum sativum), durum wheat (Triticum durum), Xanthosoma spp.; Colocasia spp., eggplant (Solanum melongena), endive (Cichorium endivia), Lygeum spartum, fennel (Foeniculum vulgare), fenugreek (Trigonella foenumgraecum), fig (Ficus carica), Corylus avellana, Furcraea macrophylla, Linum usitatissimum, Phormium tenax, Pelargonium spp., Geranium spp., Zingiber officinalis, Lagenaria spp., Cucurbita spp.), chickpeas (Cicer arietinum), grapefruit (Citrus paradise), grapes (Vitis vinifera), African grass (Lygeum spartum), orchard grass (Dactylis glomerata), peanuts (Arachis hypogaea), guava (Psidium guajava), hazel (Corylus avellana), hemp (Cannabis sativa), sunhemp (Crotalaria juncea), sedge (Agave fourcroydes), henna (Lawsonia inermis), hops (Humulus lupulus), horseradish (Armoracia rusticana), Taiwanese yew (Indigofera tinctoria), Jasminum spp., Chinese yew (Corchorus spp.), kale (Brassica oleracea acephala, kapok (Ceiba pentandra), kenaf (Hibiscus cannabinus), kohlrabi (Brassica oleracea gongylodes), lavandula spp., leek (Allium ampeloprasum), lemon (Citrus limon), lemongrass (Cymbopogon citratus), lentil (Lens culinaris), bush clover (Lespedeza spp.), lettuce (Lactuca sativa), liquorice (Glycyrrhiza glabra), Mexican lime (Citrus aurantifolia), limetta (Citrus limetta), flax (Linum usitatissimum), lychee (Litchi chinensis), loquat (Eriobotrya japonica), lupin (Lupinus spp.), Macadamia spp.), nutmeg (Myristica fragrans), Agave atrovirens, mandarin orange (Citrus reticulata), mango (Mangifera indica), cassava (Manihot esculenta), rye (Secale cereale), medlar (Mespilus germanica), melon (Cucumis melo), penicum miliaceum, finger millet (Eleusine coracana), foxtail millet (Setaria italica), barnyard grass (Echinochloa crusgalli), finger millet (Eleusine coracana); mint species (Mentha spp.), mulberry species (Morus spp.), mulberry species (Morus alba), agaricus species (Agaricus spp.); Pleurotus spp., Volvariella spp., Brassica nigra; Sinapis alba, Peach (Prunus persica), Phormium tenax, Guizotia abyssinica, Myristica fragrans, Avena spp., Elaeis guineensis, Okra (Abelmoschus esculentus), Olea europea, Papaver somniferum, Citrus sinensis, Citrus aurantium, Dactylis glomerata, Metroxylon spp.), butter palm (Borassus flabellifer), papaya (Carica papaya), parsnip (Pastinaca sativa), pear (Pyrus communis), pea (Pisum sativum), pecan (Carya illinoinensis), pepper (Capsicum annuum), persimmon (Diospyros kaki); American persimmon (Diospyros virginiana), pigeon pea (Cajanus cajan), pineapple (Ananas comosus), pineapple species (Pistacia spp.), plum (Prunus domestica), pomegranate (Punica granatum), pomelo (Citrus grandis), potato (Solanum tuberosum), sweet potato (Ipomoea batatas), pumpkin species (Cucurbita spp.), Chrysanthemum cinerariaefolium, Aspidosperma spp., Quince (Cydonia oblonga), Cinchona spp., Quinoa (Chenopodium quinoa), Radish (Raphanus sativus) (including horseradish (Cochlearia armoracia)), Boehmeria nivea, Agrostis spp., Boehmeria nivea, Rheum spp., Rice (Oryza sativa); Oryza glaberrima, Rose spp., Hevea brasiliensis, Rye (Secale cereale), Lolium spp., safflower (Carthamus tincto. rius, sago palm species (Metroxylon spp.), sainfoin (Onobrychis viciifolia), cornstarch (Valerianella locusta), rye (Tragopogon porrifolius), sapodilla (Achras sapota), mandarin orange (Citrus reticulata), cabbage (Brassica oleracea capitata), yellow rye (Scorzonera hispanica), sesame (Sesamum indicum), Butyrospermum paradoxum, sisal (Agave sislana), Mexican lime (Citrus aurantifolia), soybean (Glycine max), spelt (Triticum spelta), spinach (Spinacia oleracea), rye (Secale cereale, Cucurbita spp., Fragaria spp., Sorghum bicolor Sudanense, Sugarcane (Saccharum officinarum), Sunflower (Helianthus annuus), Sunhemp (Crotalaria juncea), Citrus limetta, Sweet potato (Ipomoea batatas), Mandarin orange (Citrus reticulata), Xanthosoma sagittifolium, Cassava (Manihot esculenta), Taro (Colocasia esculenta), Tea plant (Camellia sinensis), Eragrostis abyssinica abyssinica, Phleum pratense, Nicotiana tabacum, Lycopersicum esculentum, Lotus spp., Aleurites spp.), Brassica rapa, Urena lobata, Vanilla planifolia, Vicia sativa, Juglans spp., Watermelon (Citrullus lanatus), Black wattle (Acacia mearnsii), Triticum spp., Hordeum spp., Dioscorea spp., and Ilex paraguariensis.

[0098] Suitably, the plant or its part that can be protected by the compound, composition or agent of the present invention is selected from the plant or its part that is infested with Hemiptera, Diptera, Coleoptera, Blattodea and / or Lepidoptera insects or that attracts Hemiptera, Diptera, Coleoptera, Blattodea and / or Lepidoptera insects.Suitably, the plant or its part that is infested with Hemiptera, Diptera, Coleoptera, Blattodea and / or Lepidoptera insects or that attracts Hemiptera, Diptera, Coleoptera, Blattodea and / or Lepidoptera insects is any of those listed above.

[0099] Suitably the plant or part thereof which is infested with or attracts hemipteran insects is any of those listed above.

[0100] Suitably the plant or part thereof which is infested with or attracts dipteran insects is any of those listed above.

[0101] Suitably the plant or part thereof which is infested with or attracts lepidopteran insects is any of those listed above.

[0102] Suitably the plant or part thereof which is infested with or attracts Coleoptera insects is any of those listed above.

[0103] Suitably the plant or part thereof which is infested with or attracts cockroach insects is any of those listed above.

[0104] In one embodiment the plant or part thereof is a plant or part thereof which is infested with or attracts hemipteran insects, such as: cereals, such as wheat (Triticum spp.), oats (Avena spp.), rye (Secale spp.), barley (Hordeum spp.), rice (Oryza spp.) and maize (Zea spp.); apples (Malus spp.); pears (Pyrus spp.); strawberries (Fragaria spp.), blueberries (Vaccinium spp.), and the like. spp.), blackberries (Rubus spp.), raspberries (Rubus spp.), citrus fruits (Citrus spp.), olives (Olea spp.), durians (Durio spp.), longans (Dimocarpus spp.), lychees (L. chinensis), persimmons (Diospyros spp.), spp.); beans and peas (including but not limited to Phaseolus, Vigna, Pisum, Lens, Glycine, Cicer, Cajanus, Arachis spp.), sugar beet (Beta vulgaris), sugar cane (Saccharum spp.), lettuce (Lactuca spp.), brassicas including rapeseed (Brassica spp.), alliums (Allium spp.), tomatoes (Solanum spp.), spp.), peppers (Capsicum spp.), asparagus (Asparagus officinalis), melons, squash, pumpkins, cucumbers (Cucumis spp.)), tubers (potatoes) (Solanum spp.) and cotton (Gossypium spp.), or parts thereof.

[0105] In one embodiment, the plant or part thereof is from the Solanaceae, Cruciferae, and Leguminosae families, for example: cereals, such as wheat (Triticum spp., including winter wheat Triticum aestivum L); peaches (Prunus spp.), strawberries (Fragaria spp.), blueberries (Vaccinium spp.), blackberries (Rubus spp.), raspberries (Rubus spp.), Brassicas (Brassica spp.), such as rapeseed, lettuce (Lactuca spp.), and the like. spp.), tomatoes (Solanum spp.), peppers (Capsicum spp.), beans and peas (including but not limited to Vigna, Pisum spp.), melons, squash, pumpkins, cucumbers (Cucumis spp.), citrus fruits (Citrus spp.), tubers (potatoes) (Solanum spp.) and cotton (Gossypium spp.). In one embodiment, the plant is selected from plants or parts thereof which are subject to or attract an infestation of aphid insects, suitably an infestation of M. persicae insects, including fruit and vegetable crops, or parts thereof, including Brassica spp. In one embodiment, the plant is a vegetable crop, suitably a Brassica spp.

[0106] In one embodiment the plant or part thereof is a plant or part thereof which is infested with or attracts dipteran insects, such as: cereals (Triticum spp.); oats (Avena spp.); rye (Secale spp.); barley (Hordeum spp.), rice (Oryza spp.) and maize (Zea spp.). spp.); beans and peas (including but not limited to Phaseolus, Vigna, Pisum, Lens, Glycine, Cicer, Cajanus, Arachis spp.); apples (Malus spp.), pears (Pyrus spp.), strawberries (Fragaria spp.), blueberries (Vaccinium spp.), blackberries (Rubus spp.), raspberries (Rubus spp.), and other fruits and vegetables. spp.), cherries, plums, apricots, peaches, nectarines (Prunus spp.), blackcurrants, red currants, white currants, gooseberries (Ribes spp.), kiwi fruit (Actinidia spp.), papaya (Carica spp.), avocado (Persea spp.), mango (Mangifera indica L.), longan (Dimocarpus spp.), lychee (L. chinensis), grapes (Vitis spp.), figs (Ficus spp.), passion fruit (Passiflora spp.), fruit crops, including Japanese pears (Pyrus spp.), Japanese pears (Pyrus spp.), citrus fruits (Citrus spp.), and olives (Olea spp.); alliums (Allium spp.), eggplant, tomato (Solanum spp.) and pepper (Capsicum spp.), lettuce (Lactuca spp.), brassicas (Brassica spp.) and vegetable crops including zucchini, melon, squash, pumpkin (Cucumis spp.); root crops of the Apiaceae family including carrots (Daucus spp.), parsnips (Pastinaca spp.), or parts thereof.

[0107] In one embodiment, the plant or part thereof is a plant or part thereof that is infested with or attracts Lepidoptera insects, such as: cereals, such as wheat (Triticum spp.), oats (Avena spp.), rye (Secale spp.), barley (Hordeum spp.), rice (Oryza spp.) and maize (Zea spp.); apples (Malus spp.); pears (Pyrus spp.); nuts (e.g. almonds (P. amygdalus), pistachios (Pistacia vera), and the like. vera), walnuts (Juglandaceae), hazelnuts (Corylus spp.); avocados, including avocados (Persea Americana) (Lauraceae), blueberries (Vaccinium spp.), citrus fruits (Citrus spp.), olives (Olea spp.), durians (Durio spp.), longans (Dimocarpus spp.), lychees (L. chinensis), persimmons (Diospyros spp.), and citrus fruits (Citrus spp.). spp.); beans and peas (including but not limited to Phaseolus, Vigna, Pisum, Lens, Glycine, Cicer, Cajanus, Arachis spp.), sugar beet (Beta vulgaris), sugar cane (Saccharum spp.), lettuce (Lactuca spp.), brassicas including rapeseed (Brassica spp.), alliums (Allium spp.), tomatoes (Solanum spp.), spp.), peppers (Capsicum spp.), asparagus (A. officinalis), melons, squash, pumpkins (Cucumis spp.), and tubers (potatoes) (Solanum spp.), or parts thereof.

[0108] insect The compounds, compositions and medicaments of the invention suitably have activity against the above mentioned insects.

[0109] The compounds, compositions and medicaments of the invention may be effective against insects. For example from the phylum Arthropoda, in particular the class Arachnids, such as, for example, Acarus spp., Aceria sheldoni, Aculops spp., Aculus spp., Amblyomma spp., Amphitetranychus viennensis, Argas spp., Boophilus spp., Brevipalpus spp., Bryobia praetiosa, Centruroides spp., Chorioptes spp., Dermanyssus spp., gallinae, Dermatophagoides pteronyssius, Dermatophagoides farinae, Dermacentor spp., Eotetranychus spp., Epitrimerus pyri, Eutetranychus spp., Eriophyes spp., Halotydeus destructor, Hemitarsonemus spp., Hyalomma spp., Ixodes spp., Latrodectus spp. spp.), Loxosceles spp., Metatetranychus spp., Nuphersa spp., Oligonychus spp., Ornithodorus spp., Ornithonyssus spp., Panonychus spp.), Phyllocoptruta oleivora, Polyphagotarsonemus latus, Psoroptes spp., Rhipicephalus spp., Rhizoglyphus spp., Sarcoptes spp., Scorpio maurus, Stenotarsonemus spp., Tarsonemus spp., Tetranychus spp., Vaejovis spp., Vasates lycopersici. .

[0110] Further examples are from the order Anoplura (Phthiraptera), such as Damalinia spp., Haematopinus spp., Linognathus spp., Pediculus spp., Ptirus pubis, Trichodectes spp.

[0111] Further examples are from the order Chilopoda, for example Geophilus spp., Scutigera spp.

[0112] Further examples are from the order Coleoptera, e.g. Acalymma vittatum, Acanthoscelides obtectus, Adoretus spp., Agelastica alni, Agriotes spp., Alphitobius diaperinus, Amphimallon solstitialis, Anobium punctatum, Anoplophora spp., Anthonomus spp., Anthrenus spp. spp.), Apion spp., Apogonia spp., Atomaria spp., Attagenus spp., Bruchidius obtectus, Bruchus spp., Cassida spp., Cerotoma trifurcata, Ceutorrhynchus spp., Chaetocnema spp., Cleonus mendicus, Conoderus spp., Cosmopolites spp. spp.), Costelytra zealandica, Ctenicera spp., Curculio spp., Cryptorhynchus lapathi, Cylindrocopturus spp., Dermestes spp., Diabrotica spp., Dichocrocis spp.), Diloboderus spp., Epilachna spp., Epitrix spp., Faustinus spp., Gibbium psylloides, Hellula undalis, Heteronychus arator, Heteronyx spp., Hylamorpha elegans, Hylotrupes bajulus, Hypera postica, Hypothenemus spp. spp.), Lachnosterna consanguinea, Lema spp., Leptinotarsa ​​decemlineata, Leucoptera spp., Lissorhoptrus oryzophilus, Lixus spp., Luperodes spp., Lyctus spp., Megascelis spp., Melanotus spp., Meligethes aeneus, Melolontha spp. spp., Migdolus spp., Monochamus spp., Naupactus xanthographus, Niptus hololeucus, Oryctes rhinoceros, Oryzaephilus surinamensis, Oryzaphagus oryzae, Otiorrhynchus spp.), Oxycetonia jucunda, Mustard beetle (Phaedon cochleariae), Phyllophaga spp., Phyllotreta spp., Japanese beetle (Popillia japonica), Premnotrypes spp., Prostephanus truncatus, Psylliodes spp., Ptinus spp., Rhizobius ventralis, Rhizopertha dominica, Sitophilus spp. spp.), Sphenophorus spp., Stegobium paniceum, Sternechus spp., Symphyletes spp., Tanymecus spp., Tenebrio molitor, Tribolium spp., Trogoderma spp., Tychius spp., Xylotrechus spp.), from Zabrus spp. Suitably the compounds, compositions and agents of the invention are effective against insects such as: the bean weevil (Bruchus rufimanus), the cabbage seed weevil (Ceutorhynchus obstrictus), the cabbage stem flea beetle (Psylliodes chrysocephalus), the cabbage stem weevil (Ceutorhynchus pallidactylus), the scarab beetle larvae (Melolontha melolontha), the Colorado potato beetle (Leptinotarsa ​​decemlineata), the pea and kidney bean weevil (Sitona lineatus), the pollen beetle (Meligethes spp. It has activity against species of the order Coleoptera selected from the group consisting of the pygmy beetle (Atomaria linearis), the rapeseed stalk weevil (Ceutorhynchus picitarsis), and the click beetle larvae (Agriotes spp.).

[0113] Yet other examples are from the order Collembola, for example Onychiurus armatus.

[0114] Yet other examples are from the order Diplopoda, for example Blaniulus guttulatus.

[0115] Further examples are from the order Diptera, for example Aedes spp., Agromyza spp., Anastrepha spp., Anopheles spp., Asphondylia spp., Bactrocera spp., Bibio hortulanus, Calliphora erythrocephala, Ceratitis capitata, Chironomus spp., Chrysomyia spp., Chrysops spp., spp.), Cochliomyia spp., Contarinia spp., Cordylobia anthropophaga, Culex spp., Culicoides spp., Culiseta spp., Cuterebra spp., Dacus oleae, Dasyneura spp., Delia spp., Dermatobia hominis, Drosophila spp., Echinocnemus spp. spp.), Fannia spp., Gasterophilus spp., Glossinax spp., Haematopota spp., Hydrellia spp., Hylemyia spp., Hyppobosca spp., Hypoderma spp., Liriomyza spp., Lucilia spp., Lutzomia spp., Mansonia spp., Musca spp.), Nezara spp., Oestrus spp., Oscinella frit, Pegomyia spp., Phlebotomus spp., Phorbia spp., Phormia spp., Prodiplosis spp., Psila rosae, Rhagoletis spp., Sarcophaga spp., Simulium spp., Stomoxys spp., Tabanus spp. spp.), Tannia spp., Tetanops spp., and Tipula spp. Further examples are from the order Heteroptera, e.g. Anasa tristis, Antestiopsis spp., Boisea spp., Blissus spp., Calocoris spp., Campylomma livida, Cavelerius spp., Cimex spp., Collaria spp., Creontiades dilutus, Dasynus piperis, Dichelops furcatus, furcatus, Diconocoris hewetti, Dysdercus spp., Euschistus spp., Eurygaster spp., Heliopeltis spp., Horcias nobilellus, Leptocorisa spp.), Leptoglossus phyllopus, Lygus spp., Macropes excavatus, Miridae, Monalonion atratum, Nezara spp., Oebalus spp., Pentomidae, Piesma quadrata, Piezodorus spp., Psallus spp., Pseudacysta persea, Rhodnius spp. spp.), the cocoa stink bug (Sahlbergella singularis), Scaptocoris castanea, Scotinophora spp., Stephanitis nashi, Tibraca spp., and Triatoma spp. Further examples are from the order Homoptera, for example Acyrthosiphon spp., Acrogonia spp., Aeneolamia spp., Agonoscena spp., Aleurodes spp., Aleurolobus barodensis, Aleurothrixus spp., Amrasca spp., Anuraphis cardui, Aonidiella spp., Aphanostigma pin, Aphis spp. spp.), Asian leafhoppers, Aspidiella spp., Aspidiotus spp., Atanus spp.), potato aphid (Aulacorthum solani), Bemisia spp., wheat straw aphid (Brachycaudus helichrysi), Brachycolus spp., radish aphid (Brevicoryne brassicae), Calligypona marginata, Carneocephala fulgida, candy aphid (Ceratovacuna lanigera), family Cercopidae, Ceroplastes spp., strawberry aphid (Chaetosiphon fragaefolii), Chionaspis tegalensis tegalensis, Chlorita onukii, Chromaphis juglandicola, Chrysomphalus ficus, Cicadulina mbila, Coccomytilus halli, Coccus spp., Cryptomyzus ribis, Dalbulus spp., Dialeurodes spp., Diaphorina spp., Diaspis spp., Drosicha spp., Dysaphis spp. spp., Dysmicoccus spp., Empoasca spp., Eriosoma spp., Erythroneura spp., Euscelis bilobatus, Ferrisia spp., Geococcus coffeae, Hieroglyphus spp.), Homalodisca coagulata, Hyalopterus arundinis, lcerya spp., Idiocerus spp., Idioscopus spp., Laodelphax striatellus, Lecanium spp., Lepidosaphes spp., Lipaphis erysimi, Macrosiphum spp., Mahanarva spp., Melanaphis sacchari, Metcalfiella spp. spp.), Metopolophium dirhodum, Monellia costalis, Monelliopsis pecanis, Myzus spp., Nasonovia ribisnigri, Nephotettix spp., Nilaparvata lugens, Oncometopia spp., Orthezia praelonga, Parabemisia myricae, Paratrioza spp., Parlatoria spp., Pemphigus spp. spp.), corn planthopper (Peregrinus maidis), Phenacoccus spp., Phloeomyzus passerinii, hop aphid (Phorodon humuli), Phylloxera spp., Pinnaspis aspidistrae, Planococcus spp.), Protopulvinaria pyriformis, Mulberry scale, Pseudococcus spp., Psylla spp., Pteromalus spp., Pyrilla spp., Quadraspidiotus spp., Quesada gigas, Rastrococcus spp. Rastrococcus spp., Rhopalosiphum spp., Saissetia spp., Scaphoides titanus, Schizaphis graminum, Selenaspidus articulatus, Sogata spp., Sogatella furcifera, Sogatodes spp., Stictocephala festina, Tenalapha malayensis, Tinocallis caryaefoliae, Tomasis spp., Toxoptera spp., Trialeurodes spp., Trioza spp., Typhlocyba spp., Unaspis spp., Viteus vitifolii, Zygina spp.

[0116] Further examples are from the order Hymenoptera, for example Acromyrmex spp., Athalia spp., Atta spp., Diprion spp., Hoplocampa spp., Lasius spp., Monomorium pharaonis, Solenopsis invicta, Tapinoma spp., Vespa spp.

[0117] Still other examples are from the order Isopoda, for example, Armadillidium vulgare, Oniscus asellus, Porcellio scaber.

[0118] Further examples are from the order Isoptera, such as Coptotermes spp., Cornitermes cumulans, Cryptotermes spp., Incisitermes spp., Microtermes obesi, Odontotermes spp., Reticulitermes spp.

[0119] Further examples are from the order Lepidoptera, e.g. Acronicta major, Adoxophyes spp., Aedia leucomelas, Agrotis spp., Alabama spp., Amyelois transitella, Anarsia spp., Anticarsia spp., Argyroploce spp., Barathra brassicae, Borbo cinnara, Bucculatrix thurberiella, Bupalus pinarius, piniarius, Busseola spp., Cacoecia spp., Caloptilia theivora, Capua reticulana, Carpocapsa pomonella, Carposina niponensis, Chematobia brumata, Chilo spp., Choristoneura spp., Clysia ambiguella, Cnaphalocerus spp., Cnephasia spp., Conopomorpha spp. spp., Conotrachelus spp., Copitarsia spp., Cydia spp., Dalaca noctuides, Diaphania spp., Diatraea saccharalis, Earias spp.), Ecdytolopha aurantium, Elasmopalpus lignosellus, Eldana saccharina, Ephestia spp., Epinotia spp., Epiphyas postvittana, Etiella spp., Eulia spp., Eupoecilia ambiguella, Euproctis spp., Euxoa spp., Feltia spp., Galleria spp. mellonella, Gracilaria spp., Grapholitha spp., Hedylepta spp., Helicoverpa spp., Heliothis spp., Hofmannophila pseudospretella, Homoeosoma spp., Homona spp., Hyponomeuta padella, Kakivoria flavofasciata, Laphygma spp., Laspeyresia molesta molesta, Leucinodes orbonalis, Leucoptera spp., Lithocolletis spp., Lithophane antennata, Lobesia spp., Loxagrotis albicosta, Lymantria spp., Lyonetia spp.), Malacosoma neustria, Maruca testulalis, Mamestra brassicae, Mods spp., Mythimna separata, Nymphula spp., Oiketicus spp., Oria spp., Orthaga spp., Ostrinia spp., Oulema oryzae, Panolis flammea, Parnara spp., Pectinophora spp., Perileucoptera spp. spp., Phthorimaea spp., Phyllocnistis citrella, Phyllonorycter spp., Pieris spp., Platynota stultana, Plodia interpunctella, Plusia spp., Plutella xylostella, Prays spp., Prodenia spp., Protoparce spp., Pseudaletia spp., Soybean looper (Pseudoplusia includens), European corn borer (Pyrausta nubilalis, Rachiplusia nu, Schoenobius spp., Scirpophaga spp., Scotia segetum, Sesamia spp., Sparaganothis spp., Spodoptera spp., Stathmopoda spp.), Stomopteryx subsecivella, Synanthedon spp., Tecia solanivora, Thermesia gemmatalis, Tinea pellionella, Tineola bisselliella, Tortrix spp., Trichophaga tapetzella, Trichoplusia spp., Tuta absoluta, and Virachola spp. .

[0120] Further examples are from the order Orthoptera, such as Acheta domesticus, Dichroplus spp., Gryllotalpa spp., Leucophaea maderae, Locusta spp., Melanoplus spp., Pulex irritans, Schistocerca gregaria.

[0121] Further examples are from the order Blattodea, such as Blatta orientalis, Blattella germanica, Periplaneta americana, Periplaneta spp., Supella longipalpa, and termites from the order Isoptera, such as those from the family Termitidae.

[0122] Further examples are from the order Siphonaptera, for example Ceratophyllus spp., Ctenocephalides spp., Tunga penetrans, Xenopsylla cheopis.

[0123] Still other examples are from the order Symphyla, such as Scutigerella spp.

[0124] Further examples are from the order Thysanoptera, e.g. Anaphothrips obscurus, Baliothrips biformis, Drepanothris reuteri, Enneothrips flavens, Frankliniella spp., Heliothrips spp., Hercinothrips femoralis, Rhipiphorothrips cruentatus, Scirtothrips spp., Taeniothrips cardamoniaci, cardamoni, Thrips spp. Further examples are from the order Zygentoma (= Thysanura), e.g. Lepisma saccharina, Thermobia domestica, e.g. Lepisma saccharina, Thermobia domestica.

[0125] In a preferred embodiment, the compounds, compositions and agents of the present invention suitably have activity against insects of the orders Hemiptera, Diptera, Coleoptera, Blattodea and / or Lepidoptera. In a preferred embodiment, the compounds, compositions and agents of the present invention suitably have activity against insects of the order Hemiptera. In a preferred embodiment, the compounds, compositions and agents of the present invention suitably have activity against aphids. In one embodiment, the compounds, compositions and agents of the present invention suitably have activity against the aphid species Myzus persicae.

[0126] hemiptera insects The compounds, compositions and agents of the present invention suitably have activity against insects of the order Hemiptera, including the group including aphids, planthoppers, leafhoppers, beetles, stink bugs and cicadas. Suitably, the compounds, compositions and agents of the present invention suitably have activity against aphids.

[0127] Hemiptera are defined by characteristic mouth parts in the form of a "proboscis" that includes modified mandibles and maxillae forming a "stylet" housed within a modified lower lip.

[0128] Many insects within these groups have endogenous neuropeptides with sequence similarity to the peptides described herein, suggesting that the compounds of the invention may have activity against those insects.

[0129] The insect may belong to the suborder Sternorrhyncha, for example to the superfamily Aphidoidea (aphid superfamily), Aleyrodoidea (whiteflies), Coccoidea (scale insects), Phylloxeroidea (including the families Phylloxeridae or "phyll aphids", and Adelgidae or woolly conifer aphids), or Psylloidea (such as the white psyllid).

[0130] Thus, the insect may be an aphid, i.e., a member of the superfamily Aphidoidea. Aphids (order Hemiptera: family Aphididae) are one of the most important groups of agricultural pests and are the vectors for the transmission of approximately 50% of all insect-transmitted plant viruses. Within that superfamily, aphids are divided into the subfamilies Aiceoninae, Anoeciinae, Aphidinae, Baltichaitophorinae, Calaphidinae, Chaitophorinae, Drepanosiphinae, Eriosomatinae, Greenideinae, Hormaphidinae, Israelaphidinae, Lachninae, Rizerii, and Scutellaria. It may be part of the family Aphididae, which includes the subfamily Lizeriinae, Macropodaphidinae, Mindarinae, Neophyllaphidinae, Phloeomyzinae, Phyllaphidinae, Pterastheniinae, Saltusaphidinae, Spicaphidinae, Taiwanaphidinae, Tamaliinae and Thelaxinae.

[0131] Aphids include, for example, the genera Acyrthosiphon (e.g. Acyrthosiphon pisum), Aphis (e.g. Aphis gossypii, Aphis glycines, Aphis fabae), Diuraphis (e.g. Diuraphis noxia), Macrosiphum (e.g. Macrosiphum rosae, Macrosiphum euphorbiae), Myzus (e.g. Myzus myzus), persicae), Rhopalosiphum (e.g., Rhopalosiphum padi), Sitobion (e.g., Sitobion avenae), or Nasonovia ribisnigri.

[0132] The peach aphid (Myzus persicae) (peach and potato aphid) is the most economically important aphid crop pest worldwide, with a global distribution and host range that encompasses over 400 species in 40 different plant families. For example, it is a major pest of agricultural crops, including fruit and potato, and acts as a vector for viruses.

[0133] Macrosiphum rosae (rose aphid) is an important horticultural pest, especially of cultivated species of the genus Rosa, and is a vector for the transmission of 12 plant viruses, including strawberry mild yellow edge virus.

[0134] The cotton aphid (Aphis gossypii) (cotton or melon aphid) is a pest of Curcibitae and cotton. The black bean aphid (Aphis fabae) is a pest of sugar beet, beans, and celery. The lettuce aphid (Nasonovia ribisnigri) (gooseberry aphid) is a pest of lettuce, gooseberry, and gooseberry. The wheat curl aphid (Rhopalosiphum padi) (bird cherry oat aphid) is a pest of cereals such as barley, oats, and wheat.

[0135] Besides aphids, the insects may be, for example, from the family Adelgidae, such as the genus Adelges (eg, Adelges tsugae).

[0136] The insect may be of the family Aleyrodidae, for example of the genus Bemisia (eg, Bemisia tabaci) or Trialeurodes (eg, Trialeurodes vaporariorum).

[0137] The insect may be of the superfamily Psylloidea, for example, of the genus Pachypsylla (e.g., Pachypsylla venusta).

[0138] As an example of a Hemipteran insect outside the order Sternorrhyncha, the insect may be of the family Cimicidae, such as the genus Cimex (bedbugs), for example Cimex lectularius.

[0139] The insect may be of the family Cicadellidae, for example the genus Cuerna (e.g. Cuerna arida), Graminella (e.g. Graminella nigrifrons) or Homalodisca (e.g. Homalodisca vitripennis). Also included in the family Cicadellidae is the green leafhopper Amrasca biguttula.

[0140] The insect may be of the Delphacidae family, such as the Nilaparvata (e.g., Nilaparvata lugens) or Sogatella (e.g., Sogatella furcifera) genus. For example, Nilaparvata lugens (brown planthopper) is a pest of rice crops, particularly in Asia.

[0141] The insects may be from the family Liviidae, for example, the genus Diaphorina (eg, Diaphorina citri).

[0142] The insect may be of the family Miridae, for example of the genus Pseudatomoscelis (e.g. Pseudatomoscelis seriatus), Lygus (e.g. Lygus hesperus) or Tupiocoris (e.g. Tupiocoris notatus). For example, the cotton flea beetle Pseudatomoscelis seriatus (cotton flea beetle) is a pest of cotton.

[0143] Insects may be from the family Pentatomidae, for example the genera Acrosternum (e.g. Acrosternum hilare), Banasa (e.g. Banasa dimiata), Euschistus (e.g. Euschistus servus, Euschistus heroes), Halyomorpha (e.g. Halyomorpha halys), Murgantia (e.g. Murgantia histrionica), Nezara (e.g. Nezara nemalus), viridula), Plautia (e.g., Plautia stali), or Podisus (e.g., Podisus maculiventris). For example, Acrosternum hilare (green stink bug) is an important pest of cotton. Euschistus servus (brown stink bug) is a pest of many agricultural crops including seeds, grains, nuts, and fruits, especially in the southern United States. Nezara viridula is a pest of grain and soybean crops, especially in Brazil.

[0144] The insect may be of the family Pyrrhocoridae, for example, of the genus Pyrrhocoris (e.g., Pyrrhocoris apterus).

[0145] The insect may be of the family Reduviidae, for example of the genus Rhodnius (e.g., Rhodnius prolixus), or of the genus Triatoma (e.g., Triatoma infestans). Rhodnius prolixus is a vector of a human disease (Chagas disease).

[0146] The insect may be of the family Triozidae, for example, of the genus Acanthocasuarina (e.g., Acanthocasuarina muellerianae).

[0147] In one embodiment, the insect may be selected from the following species: H. halys, E. heroes, A. hilare, A. gossypii, E. servus, M. persicae, N. viridula, N. lugens, P. seriatus, R. prolixus, A. fabae, R. padi, and N. ribisnigri.

[0148] In one embodiment, the insect is of the species M. persicae. In one embodiment, the insect is of the species Aphis gossypii. In one embodiment, the insect is of the species Aphis fabae. In one embodiment, the insect is of the species Rhopalosiphum padi. ​​In one embodiment, the insect is of the species Nasonovia ribisnigri.

[0149] Diptera insects The compounds, compositions and medicaments of the invention may have activity against insects of the order Diptera.

[0150] In particular, they may have activity against fruit flies, including insects of the Drosophilidae family, such as those of the Drosophila genus, for example Drosophila suzukii. They may also have activity against insects of the family Tephritidae, including those of the genera Anastrepha (Anastrepha spp.); Bactrocera (Bactrocera spp.); Ceratitis (Ceratitis spp.); Dacus (Dacus spp.); Rhagoletis (Rhagoletis spp.); Tephrititis (Tephritis spp.).

[0151] The families Drosophilidae and Tephritidae together are commonly referred to as fruit flies.

[0152] The compounds, compositions and agents are also useful in the control of other important dipteran pests, such as flies of the family Chloropidae (Chloropidae) and the genera: Phytomyza (e.g., Phytomyza angelicastri); Genus Melani (e.g., Melani agromyza); Antherigona (e.g., Antherigona spp.); Delia (e.g., Delia radicum); Contarinia (e.g., Contarinia sorghicola) may have activity against;

[0153] For further details on these and other examples, see (Non-Patent Document 2).

[0154] Lepidoptera insects The compounds, compositions and medicaments of the invention may have activity against insects of the order Lepidoptera.

[0155] In particular, they may have activity against insects of the genera: Heliothis, Plutella, Spodoptera, and Cydia. Suitably, the compounds, compositions and agents of the invention may have activity against the species: Heliothis peltigera, H. virescens, Spodoptera spp. and Cydia pomonella (codling moth), larvae of Heliothis spp. (including peltigera and virescens, Spodoptera littoralis) (representing a wide variety of moth species in the subfamily Heliothinae and genus Spodoptera, which are agricultural pests worldwide), and Plutella xylostella (diamondback moth, the most important global pest of plants in the genus Brassica).

[0156] In one embodiment, the compounds, compositions and medicaments of the invention may have activity against the diamondback moth (Plutella xylostella).

[0157] Coleoptera insect The compounds, compositions and medicaments of the invention may have activity against insects of the order Coleoptera.

[0158] In particular, they may have activity against insects of the genera: Bruchus, Ceutorhynchus, Psylliodes, Leptinotarsa, Sitona, Meligethes, Atomaria, and Agriotes. Suitably the compounds, compositions and medicaments of the invention are effective against insects such as: bean weevils (Bruchus rufimanus), cabbage seed weevils (Ceutorhynchus obstrictus), cabbage stem flea beetles (Psylliodes chrysocephalus), cabbage stem weevils (Ceutorhynchus pallidactylus), scarab beetle larvae (Melolontha melolontha), Colorado potato beetles (Leptinotarsa ​​decemlineata), pea and kidney bean weevils (Sitona lineatus), pollen beetles (Meligethes spp.), and the like. spp.), pygmy beetle (Atomaria linearis), rapeseed stalk weevil (Ceutorhynchus picitarsis), as well as click beetle larvae (Agriotes spp.).

[0159] Cockroach Insects The compounds, compositions and agents of the invention may have activity against insects of the order Blattodea.

[0160] In particular, they may have activity against insects of the infraorder Isoptera.Suitably, the compounds, compositions and agents of the invention may have activity against species of the family Termitidae.

[0161] Suitably, the compounds, compositions and agents of the invention may have activity against the species: Blatta orientalis, Blattella germanica, Periplaneta america, Periplaneta spp., Supella longipalpa.

[0162] Household pests The compounds, compositions and agents of the present invention may also have activity against household pests, such as cockroaches and termites (e.g., those of the Termitidae family). Of the more than 3000 species, these may include the German cockroach (Blattella germanica), the Oriental cockroach (Blatta orientalis), the American cockroach (Periplaneta americana) and the Asian cockroach (Supella longipalpa). Cockroaches are common household pests worldwide and can carry a variety of diseases. Control of these and other household pests (e.g., ants) is envisioned, in particular, by treating surfaces that insects move on with food bait containing the compounds, compositions and agents of the present invention by direct spray application of the compounds, compositions and agents of the present invention.

[0163] Thus, a further aspect of the present invention may include a bait comprising the compound or composition of the present invention, which may suitably be a bait for domestic pests. A further aspect of the present invention may include a method for controlling domestic pests, reducing domestic pest populations, inhibiting domestic pest populations, or increasing the mortality rate of domestic pests, which comprises treating a surface (e.g., wood) that domestic pests contact with, or contacting domestic pests with, a compound or composition of the present invention. Further details of such methods are described herein below. Optionally, treating or contacting may comprise by suitable means of application, such as spraying, as described elsewhere herein. Suitably, sprayable formulations comprising the compound or composition of the present invention are also envisaged. Suitable formulations are described elsewhere herein.

[0164] Methods and uses of the present invention Methods for increasing insect mortality The present invention provides a method of increasing insect mortality comprising contacting an insect or insect population with a compound, composition or combination described herein. The insect or insect population may be Hemiptera, Diptera, Coleoptera, Blattodea, and / or Lepidoptera insects.

[0165] In one embodiment, there is provided a method of increasing mortality of dipteran insects comprising contacting a dipteran insect or a population of dipteran insects with a compound or composition or combination of the present invention.

[0166] In one particular embodiment, there is provided a method of increasing mortality in Drosophila suzukii comprising contacting the insects or population of insects with a compound or composition or combination of the present invention.

[0167] In one embodiment, there is provided a method of increasing mortality in hemipteran insects comprising contacting a hemipteran insect or a population of hemipteran insects with a compound or composition or combination as defined herein.

[0168] In a particular embodiment, there is provided a method of increasing aphid mortality comprising contacting an aphid insect or insect population with a compound or composition or combination as defined herein.

[0169] In a particular embodiment, the method of preventing or inhibiting the growth of aphids, such as Aphis fabae, Aphis gossypii, Acyrthosiphon pisum, Myzus persicae, Amrasca biguttula, Rhopalosiphum padi, or Nasonovia ribisnigri, comprises contacting an insect or population of insects with a compound or composition or combination as defined herein. The present invention provides a method for increasing the mortality rate of Rhopalosiphum padi, lettuce aphid, or rice aphid.

[0170] In a particular embodiment, there is provided a method of increasing mortality of Myzus persicae, comprising contacting a Myzus persicae insect or insect population with a compound or composition or combination as defined herein.

[0171] In a particular embodiment, there is provided a method of increasing mortality of Rhopalosiphum padi comprising contacting Rhopalosiphum padi insects or insect populations with a compound or composition or combination as defined herein.

[0172] In a particular embodiment, there is provided a method of increasing mortality of Nasonovia ribisnigri insects (Nasonovia ribisnigri), comprising contacting the insects or insect population with a compound or composition or combination as defined herein.

[0173] In one embodiment, there is provided a method of increasing mortality in Lepidoptera insects comprising contacting a Lepidoptera insect or a population of Lepidoptera insects with a compound or composition or combination as defined herein.

[0174] In a particular embodiment, there is provided a method of increasing mortality of Plutella xylostella comprising contacting Plutella xylostella insects or insect populations with a compound or composition or combination as defined herein.

[0175] In one embodiment, there is provided a method of increasing mortality of a Coleoptera insect, comprising contacting the Coleoptera insect or a population of Coleoptera insects with a compound or composition or combination as defined herein.

[0176] In one embodiment, there is provided a method for increasing mortality of a cockroach insect, comprising contacting the cockroach insect or a population of cockroach insects with a compound or composition or combination as defined herein.

[0177] Methods for inhibiting or reducing infestation of plants or sites The present invention further provides a method of inhibiting infestation of a plant or plant part by insects, suitably Hemiptera, Diptera, Coleoptera, Blattophila and / or Lepidoptera insects, comprising contacting the plant or plant part with a compound, composition or combination as described.

[0178] In one embodiment, there is provided a method of inhibiting infestation of a plant by a dipteran insect comprising contacting the plant with a compound or composition or combination of the present invention.

[0179] In a particular embodiment, there is provided a method of inhibiting infestation of a plant by Drosophila suzukii comprising contacting the plant with a compound or composition or combination of the present invention.

[0180] In one embodiment, there is provided a method of inhibiting infestation of a plant by a hemipteran insect, comprising contacting the plant with a compound or composition or combination as defined herein.

[0181] In one embodiment there is provided a method of inhibiting aphid infestation of a plant comprising contacting the plant with a compound or composition or combination as defined herein.

[0182] In one embodiment, there is provided a method of inhibiting infestation of a plant by Aphis fabae, Aphis gossypii, Acyrthosiphon pisum, Myzus persicae, Rhopalosiphum padi, or Nasonovia ribisnigri, comprising contacting the plant with a compound or composition or combination as defined herein.

[0183] In a particular embodiment, there is provided a method of inhibiting infestation of a plant by Rhopalosiphum padi, comprising contacting the plant with a compound or composition or combination as defined herein.

[0184] In a particular embodiment, there is provided a method of inhibiting infestation of a plant by the lettuce aphid (Nasonovia ribisnigri), comprising contacting the plant with a compound or composition or combination as defined herein.

[0185] In one embodiment, there is provided a method of inhibiting infestation of a plant by Myzus persicae, comprising contacting the plant with a compound or composition or combination as defined herein.

[0186] In one embodiment, there is provided a method of inhibiting infestation of a plant by Halyomorpha halys, comprising contacting the plant with a compound or composition or combination as defined herein.

[0187] In one embodiment, there is provided a method of inhibiting infestation of a plant by a lepidopteran insect, comprising contacting the plant with a compound or composition or combination as defined herein.

[0188] In one embodiment, there is provided a method of inhibiting infestation of a plant by the diamondback moth (Plutella xylostella) comprising contacting the plant with a compound or composition or combination as defined herein.

[0189] In one embodiment, there is provided a method of inhibiting infestation of a plant by a Coleoptera insect, comprising contacting the plant with a compound or composition or combination as defined herein.

[0190] In one embodiment, there is provided a method of inhibiting infestation of a plant by cockroach insects comprising contacting the plant with a compound or composition or combination as defined herein.

[0191] The present invention further provides a method of inhibiting infestation by insects, suitably Hemiptera, Diptera, Coleoptera, Blattodea and / or Lepidoptera insects, of a site in which plants are growing or intended to grow, comprising contacting the site with a compound, composition or combination as described.

[0192] The method can be prophylactic, thus for example, a compound can be applied to a plant or plant part, or to a site while the plant or part, or field, is free or substantially free of insects.

[0193] Suitably, the site may be any agricultural site suitable for growing plants. Suitably, the site may be any area or location suitable for growing plants or where plants are growing. Suitable sites may include cultivated land, brown ground sites, farm fields, greenhouses, storage sheds, containers, aquaponics and hydroponics systems, etc. In one embodiment, the site is a farm field.

[0194] Alternatively, the plant or plant part or site may already be colonised or infested by insects, suitably Hemiptera, Diptera, Coleoptera, Blattophila and / or Lepidoptera insects.

[0195] Thus, the present invention further provides a method of reducing insect infestation of a plant or plant part, or reducing the insect load on a plant or plant part, comprising contacting the plant or plant part with a compound, composition, or combination described herein.The present invention also provides a method of reducing insect infestation of a field, or reducing the insect load in a field, comprising contacting the field with a compound, composition, or combination described herein.Suitably, the insects are selected from the group consisting of Hemiptera, Diptera, Coleoptera, Blattella and / or Lepidoptera.

[0196] Methods for reducing insect feeding The present invention further provides a method of reducing insect feeding, comprising contacting an insect or insect population with a compound, composition or combination described herein. Suitably, reducing insect feeding on a plant or plant part. The insect or insect population may be Hemiptera, Diptera, Coleoptera, Blattodea and / or Lepidoptera insects.

[0197] How to protect plants from insects The present invention further provides a method of protecting a plant or part thereof from insects or insect infestation, and in particular a method of protecting a plant or part thereof against Hemiptera, Diptera, Coleoptera, Blattophila and / or Lepidoptera insects or their infestation, which method comprises the step of directly or indirectly applying to the plant or part of the plant an insecticidal compound or composition or combination of the present invention. Suitably, the indirect applying may comprise applying the compound or composition or combination of the present invention to a field or locus.

[0198] The present invention also provides a post-harvest treatment method for protecting or treating a harvested plant or harvested part of a plant against insects or insect infestations, in particular against Hemiptera, Diptera, Coleoptera, Blattophila and / or Lepidoptera insects or infestations thereof, which comprises applying to the harvested plant or harvested part of a plant, directly or indirectly, an insecticidal compound or composition or combination of the present invention under conditions effective to protect or treat the harvested plant or harvested part of a plant against insects. Suitably indirectly applying may comprise applying a compound or composition or combination of the present invention to the location where the plant or harvested part of the plant is stored or intended to be stored.

[0199] Suitably, the insects may be from the orders Hemiptera, Diptera, Coleoptera, Blattodea and / or Lepidoptera.

[0200] Method of contacting insects In one embodiment, there is provided a method of contacting an insect with a compound, preferably an insect control agent, even more preferably an insecticide, said method comprising applying a compound or composition or combination according to the present invention at or on a site frequented by the insect.

[0201] The site frequented by insects may be the natural habitat of the insects or a place where the insects regularly visit. The site can then be treated with the above-mentioned compound or composition. As a non-limiting example, a mosquito net impregnated with an encapsulated insecticide can be used as the application method. Alternatively, the site is generated by application of a visual attractant or attractant for insects. Visual attractants are known to those skilled in the art and include, but are not limited to, light sources, colored objects, and shapes or silhouettes that stand out against a contrasting background. As mentioned above, insect attractants include, but are not limited to, pheromones, kairomones, and allomones. The attractant can be present in the composition or it can be applied separately from the compound or composition or combination to ensure that the insects are attracted to the site where the compound or composition or combination is applied.

[0202] Suitably, the insect may be of the order Hemiptera, Diptera, Coleoptera, Blattodea and / or Lepidoptera. More suitably, the insect may be of the order Hemiptera. Most suitably, the insect is an aphid, such as Myzus persicae.

[0203] Application of the Compound or Composition The compound or composition or combination of the present invention may be contacted with an insect or insect population, suitably this may include directly applying the compound or composition or combination to the insect or insect population. For example, it may be applied topically. Alternatively, the compound or composition or combination may be applied indirectly. For example, it may be applied to a substrate, site or location that may contact the insect or insect population. The substrate may be a plant or a part of a plant, particularly for Hemiptera or Diptera or Coleoptera or Lepidoptera or Blattodea, which represents a pest of plants (crops or horticultural plants), or suitably the field, location or area where the plant is growing. Suitably therefore, the compound or composition or combination may be applied to the plant or a part of a plant. Suitably therefore, the compound or composition or combination may be applied to the site where the plant is growing.

[0204] However, for insects that represent pests to humans that may be vectors of human disease, such as the Cimicidae (e.g., Cimex bedbugs, e.g., Cimex lectularius) or Reduviidae (e.g., Rhodnius, e.g., Rhodnius prolixus, or Triatoma, e.g., Triatoma infestans), the substrate may be a household surface or item, such as bedding, a mattress, or any other suitable household surface. The compound or composition may be applied to the substrate in a form suitable for ingestion by the insect.

[0205] Suitably, contacting may include, for example, feeding or spraying. Suitably, feeding may be aided via a bait attractant which may be included in the compositions of the invention, as described below.

[0206] The method may include, for example, but not limited to, contacting or applying a compound or composition or combination disclosed herein directly or indirectly to the plant or plant part at a rate of more than 10 g of compound per hectare, for example, at a rate of more than 24 g of compound per hectare, for example, at a rate of more than 50 g of compound per hectare, for example, at a rate of more than 75 g of compound per hectare, for example, at a rate of more than 100 g of compound per hectare, or in particular at a rate of more than 5 g of compound per hectare, such as at a rate of more than 200 g of compound per hectare. These methods may include applying a compound, composition or combination disclosed herein directly or indirectly to a plant or part of a plant, for example at a rate of 5 g to 100 g of compound, composition or combination per hectare, including but not limited to, at a rate of 5 g to 200 g of compound, composition or combination per hectare, particularly at a rate of 5 g to 50 g of compound, composition or combination per hectare, such as 5 g to 30 g of compound, composition or combination per hectare, or at a rate of 10 g to 25 g per hectare.

[0207] The compounds or compositions or combinations disclosed herein may be directly or indirectly contacted / applied to the plant or plant parts, optionally after harvest, by spraying, atomizing, foaming, fogging, cultivating in hydroculture, cultivating in hydroponics, coating, submerging, injecting and / or dusting. Suitably, the contacting may include, for example, feeding or spraying. In some embodiments, the contacting is by feeding. The contacting may include injecting the plant (e.g., tree) or parts thereof with the composition defined herein, using systems and methods, for example, those described in U.S. Pat. No. 5,399,623; U.S. Pat. No. 5,493,361; U.S. Pat. No. 5,523,636; U.S. Pat. No. 5,633,396; U.S. Pat. No. 5,711,363 ... and U.S. Pat. No. 5,711,363, the entire contents of which are incorporated by reference.

[0208] Suitably, the compound may be contacted with the insect or insect population, or the plant or plant part, at any suitable concentration that is effective. Suitably, the compositions and combinations may contain such an effective concentration of the compound. Suitably, the concentration of the compound may be from 10 to 200 mg / kg. -3 ~10 -9 M, appropriately, 10 -4 ~10 -6 M, appropriately, 10 -4 ~10 -5 It's M.

[0209] Use as a plant protection agent The present invention further provides the use of the compounds, compositions or combinations described herein as plant protection agents, in particular for protecting plants or plant parts against insects, suitably against Hemiptera, Diptera, Coleoptera, Blattophila and / or Lepidoptera insects. Plant protection agents are further described herein above.

[0210] Use as an insect control agent The present invention provides the use of a compound or composition or combination thereof as described herein as an insect control agent, particularly in a method for increasing mortality in insects or inhibiting infestation of plants by insects.

[0211] The present invention also provides the use of a compound or composition or combination thereof as described herein as an insect control agent, particularly in a method of increasing mortality of Hemiptera, Diptera, Coleoptera, Blattodea and / or Lepidoptera insects, or in a method of inhibiting or reducing infestation or reducing the insect load of a plant by insects, suitably by Hemiptera, Diptera, Coleoptera, Blattodea and / or Lepidoptera insects.

[0212] The present invention also provides the use of the compounds or compositions or combinations thereof described herein as insect control agents, in particular by having a biostatic effect on Hemiptera, Diptera, Coleoptera, Blattodea and / or Lepidoptera insects, a biocidal effect on Hemiptera, Diptera, Coleoptera, Blattodea and / or Lepidoptera insects, and / or a pesticidal effect on Hemiptera, Diptera, Coleoptera, Blattodea and / or Lepidoptera insects.

[0213] "Biostatic (effect)" or "biostatic use" as used herein includes the effect or use of a compound or composition or combination described herein (optionally included in a biostatic, biocidal, fungicidal or fungistatic composition as defined herein) to control, regulate or interfere with the harmful activity of a pest, e.g., a plant pest or a plant pathogen. Suitably, the pest is of the insect orders Hemiptera, Diptera, Coleoptera, Blattella and / or Lepidoptera. Suitably, includes, but is not limited to, inhibiting insect growth or activity, altering insect behavior, repelling or attracting insects to plants, plant parts or other agriculturally related settings, e.g., for home use or in the soil.

[0214] "Pesticidal activity" or "biocidal activity", as used interchangeably herein, means killing or severely damaging a pest. Suitably, this may be the same as insecticidal activity, where the pest is an insect. Suitably, the compound, composition or combination may be used as an insect control agent, where the insect encodes a pyrokinin peptide.

[0215] Suitably, the compound or composition or combination may be used as an insect control agent, wherein the insect is of the Diptera order.Suitably, the compound may be used as an insect control agent, wherein the insect is of the Drosophila genus.Suitably, the compound may be used as an insect control agent, wherein the insect is Drosophila suzukii.

[0216] Suitably, the compound or composition or combination as defined herein may be used as an insect control agent, wherein the insect is of the order Hemiptera. Suitably, the compound or composition or combination as defined herein may be used as an insect control agent, wherein the insect is an aphid. Suitably, the compound or composition or combination as defined herein may be used as an insect control agent, wherein the insect is of the genus Myzus. Suitably, the compound or composition or combination as defined herein may be used as an insect control agent, wherein the insect is Myzus persicae.

[0217] Suitably, the compound or composition or combination as defined herein may be used as an insect control agent, wherein the insect is of the order Hemiptera. Suitably, the compound or composition or combination as defined herein may be used as an insect control agent, wherein the insect is an aphid. Suitably, the compound or composition or combination as defined herein may be used as an insect control agent, wherein the insect is of the genus Rhopalosiphum. Suitably, the compound or composition or combination as defined herein may be used as an insect control agent, wherein the insect is Rhopalosiphum padi.

[0218] Suitably, the compound or composition or combination as defined herein may be used as an insect control agent, wherein the insect is of the order Hemiptera. Suitably, the compound or composition or combination as defined herein may be used as an insect control agent, wherein the insect is an aphid. Suitably, the compound or composition or combination as defined herein may be used as an insect control agent, wherein the insect is of the genus Aphis. Suitably, the compound or composition or combination as defined herein may be used as an insect control agent, wherein the insect is Aphis gossypii or Aphis fabae.

[0219] Suitably, the compound or composition or combination as defined herein may be used as an insect control agent, wherein the insect is of the order Hemiptera. Suitably, the compound or composition or combination as defined herein may be used as an insect control agent, wherein the insect is an aphid. Suitably, the compound or composition or combination as defined herein may be used as an insect control agent, wherein the insect is of the genus Nasonovia. Suitably, the compound or composition or combination as defined herein may be used as an insect control agent, wherein the insect is the lettuce long-horn aphid (Nasonovia ribisnigri).

[0220] Suitably, the compound or composition or combination as defined herein may be used as an insect control agent, wherein the insect is of the order Hemiptera. Suitably, the compound or composition or combination as defined herein may be used as an insect control agent, wherein the insect is of the genus Halyomorpha. Suitably, the compound or composition or combination as defined herein may be used as an insect control agent, wherein the insect is Halyomorpha halys.

[0221] Suitably, the compound or composition or combination as defined herein may be used as an insect control agent, wherein the insect is of the order Lepidoptera. Suitably, the compound or composition or combination as defined herein may be used as an insect control agent, wherein the insect is of the genus Plutella. Suitably, the compound or composition or combination as defined herein may be used as an insect control agent, wherein the insect is Plutella xylostella.

[0222] Suitably, the compounds or compositions or combinations defined herein may be used as insect control agents, wherein the insects are of the order Coleoptera.

[0223] Suitably, the compounds or compositions or combinations defined herein may be used as insect control agents, where the insect is of the order Blattodea. Suitably, the compounds or compositions or combinations defined herein may be used as insect control agents, where the insect is a cockroach or a termite.

[0224] Methods for controlling insect reproduction The present invention also provides the insecticidal compounds, compositions and combinations described herein for controlling the fertility of insect species. Suitably, the insect is selected from Hemiptera, Diptera, Coleoptera or Lepidoptera, such as those described elsewhere herein. Suitably, in some embodiments, the Hemiptera insect is Myzus persicae. Suitably, in some embodiments, the Dipteran insect is D. suzukii. Suitably, in some embodiments, the Lepidoptera insect is Plutella xylostella.

[0225] Also provided is a method of controlling hemipteran insect fecundity, comprising contacting a substrate, such as a plant or soil, with a compound of the invention, or a composition of the invention. Suitably, the hemipteran insect is any of those disclosed herein, such as an aphid.

[0226] Also provided is a method of controlling the fecundity of dipteran insects, comprising contacting a substrate, such as a plant or soil, with a compound of the invention, or a composition of the invention. Suitably, the dipteran insect is any of those disclosed herein.

[0227] Also provided is a method of controlling lepidopteran insect fecundity, comprising contacting a substrate, such as a plant or soil, with a compound of the invention, or a composition of the invention. Suitably, the lepidopteran insect is any of those disclosed herein.

[0228] Also provided is a method of controlling the fertility of Coleoptera insects, comprising contacting a substrate, such as a plant or soil, with a compound of the invention, or a composition of the invention. Suitably, the Coleoptera insects are any of those disclosed herein.

[0229] Also provided is a method of controlling the fertility of a cockroach insect, the method comprising contacting a substrate, such as a plant or soil, with a compound of the invention, or a composition of the invention. Suitably, the cockroach insect is any of those disclosed herein.

[0230] Also provided is a method of controlling hemipteran insect fecundity, comprising contacting a substrate, such as a plant or soil, with a combination as described herein. Suitably, the hemipteran insect is any of those disclosed herein. Suitably, the combination comprises a compound of the invention and a kinin peptide, or an analog thereof.

[0231] Also provided is a method of controlling the fecundity of dipteran insects, comprising contacting a substrate, such as a plant or soil, with a combination as described herein. Suitably, the dipteran insect is any of those disclosed herein. Suitably, the combination comprises a compound of the invention and a kinin peptide, or an analog thereof.

[0232] Also provided is a method of controlling lepidopteran insect fertility, comprising contacting a substrate, such as a plant or soil, with a combination as described herein or a composition of the present invention. Suitably, the lepidopteran insect is any of those disclosed herein. Suitably, the combination comprises a compound of the present invention and a kinin peptide, or an analog thereof.

[0233] Also provided is a method of controlling the fertility of Coleoptera insects, comprising contacting a substrate, such as a plant or soil, with a combination as described herein or a composition of the present invention. Suitably, the Coleoptera insects are any of those disclosed herein. Suitably, the combination comprises a compound of the present invention and a kinin peptide, or an analog thereof.

[0234] Also provided is a method of controlling the fecundity of cockroach insects, comprising contacting a substrate, such as a plant or soil, with a combination as described herein or a composition of the present invention. Suitably, the cockroach insect is any of those disclosed herein. Suitably, the combination comprises a compound of the present invention and a kinin peptide, or an analog thereof.

[0235] There is also provided a method of controlling the fecundity of a hemipteran insect or insect population, the method comprising contacting a hemipteran insect or insect population with a compound of the invention, or a composition of the invention. Suitably the hemipteran insect is any of those disclosed herein.

[0236] There is also provided a method of controlling the fecundity of a dipteran insect or insect population, comprising contacting a dipteran insect or insect population with a compound of the invention, or a composition of the invention. Suitably, the dipteran insect is any of those disclosed herein.

[0237] There is also provided a method of controlling the fecundity of a lepidopteran insect or insect population, comprising contacting the lepidopteran insect or insect population with a compound of the invention, or a composition of the invention. Suitably the lepidopteran insect is any of those disclosed herein.

[0238] There is also provided a method of controlling the fertility of a Coleoptera insect or insect population, comprising contacting the Coleoptera insect or insect population with a compound of the invention, or a composition of the invention. Suitably the Coleoptera insect is any of those disclosed herein.

[0239] Also provided is a method of controlling the fecundity of a cockroach insect or insect population, comprising contacting a cockroach insect or insect population with a compound of the invention, or a composition of the invention. Suitably, the cockroach insect is any of those disclosed herein.

[0240] Also provided is a method of controlling the fecundity of a hemipteran insect or insect population, comprising contacting a hemipteran insect or insect population with a combination as described herein. Suitably, the hemipteran insect is any of those disclosed herein. Suitably, the combination comprises a compound of the invention and a kinin peptide, or an analogue thereof.

[0241] Also provided is a method of controlling the fecundity of a dipteran insect or insect population, comprising contacting a dipteran insect or insect population with a combination as described herein. Suitably, the dipteran insect is any of those disclosed herein. Suitably, the combination comprises a compound of the invention and a kinin peptide, or an analogue thereof.

[0242] Also provided is a method of controlling the fecundity of a lepidopteran insect or insect population, comprising contacting a lepidopteran insect or insect population with a combination as described herein, or a composition of the present invention. Suitably, the lepidopteran insect is any of those disclosed herein. Suitably, the combination comprises a compound of the present invention and a kinin peptide, or an analogue thereof.

[0243] Also provided is a method of controlling the fertility of a Coleoptera insect or insect population, comprising contacting a Coleoptera insect or insect population with a combination as described herein or a composition of the present invention. Suitably, the Coleoptera insect is any of those disclosed herein. Suitably, the combination comprises a compound of the present invention and a kinin peptide, or an analog thereof.

[0244] Also provided is a method of controlling the fecundity of a cockroach insect or insect population, comprising contacting a cockroach insect or insect population with a combination as described herein or a composition of the present invention. Suitably, the cockroach insect is any of those disclosed herein. Suitably, the combination comprises a compound of the present invention and a kinin peptide, or an analogue thereof.

[0245] In the context of the present invention, "controlling reproduction" refers to reducing, inhibiting, or eliminating the presence of an insect species during one or more of its developmental stages. For example, the compositions of the present invention may be used to control the development of mites in any stage, such as egg, larva, nymph, and adult forms.

[0246] Combination with further insecticides The compounds of the present invention may be used in combination with one or more additional insecticides or pesticidal compounds, such as those described herein. Also provided are combinations comprising a compound of the present invention, or a salt or solvate thereof, in combination with one or more additional active insecticides or pesticidal compounds.

[0247] The compositions of the present invention may further comprise one or more additional active insecticides or active insecticidal compounds.

[0248] Suitably, the insecticide may be selected from insect neuropeptides or analogues thereof, such as kinin peptides, AKH peptides, DH31 peptides, DH44 peptides, pyrokinin peptides or CAPA peptides (e.g. CAPA-1, CAPA-2 or CAPA-3 analogues). In a particular embodiment, the further insecticide is a kinin peptide, such as SB-P-69 ([Hy]-NFSPWG-[NH2], SEQ ID NO: 14). Additionally or alternatively, the insecticide may be a chemical insecticide, for example: pyrethroids (permethrin, cypermethrin, deltamethrin); organophosphates (malathion, chlorpyrifos, diazinon); neonicotinoids (imidacloprid, clothianidin, thiamethoxam); carbamates (carbaryl, methomyl, propoxur); botanical insecticides (pyrethrins (derived from chrysanthemum), rotenone (derived from the roots of certain plants)); biopesticides (Bacillus thuringiensis (Bt) products, Beauveria bassiana (fungus), Metarhizium anisopliae (Metarhizium anisopliae) (fungi); insect growth regulators (IGRs) (methoprene, pyriproxyfen); fipronil; spinosad; avermectins (including abamectin and ivermectin); chitin synthesis inhibitors (diflubenzuron, hexaflumuron); piperonyl butoxide; flonicamid; indoxacarb; and sulfoxaflor.

[0249] Suitably, said further insecticide or insecticidal compound may be included in the composition of the present invention.

[0250] The method of the invention may further comprise contacting the insect population or the plant or part thereof with a further insecticide or insecticidal compound, such as those described herein. Suitably the further insecticide or insecticidal compound is a kinin peptide.

[0251] Suitably, reference herein to a compound of the invention or a composition thereof may equivalently refer to a combination of a compound of the invention with one or more pesticides or pesticidal compounds, or to a composition containing such a combination.

[0252] Suitably, there is provided a combination comprising a compound of the invention, or a salt or solvate thereof, in combination with one or more of the peptides listed in the table below.

[0253] [Table 2]

[0254] In one embodiment, the compounds of the present invention are utilized in combination with further pyrokinin peptides, such as:

[0255] [Table 3]

[0256] In one embodiment, the compounds of the present invention are utilized in combination with kinin peptides such as:

[0257] [Table 4]

[0258] In one embodiment, the compounds of the present invention are utilized in combination with a CAPA peptide (eg, a CAPA2 peptide).

[0259] In one embodiment, the compounds of the present invention are utilized in combination with an AKH peptide, such as:

[0260] [Table 5]

[0261] Suitably any of the above combinations of compounds may be included in a composition of the present invention.

[0262] The choice of supplemental or additional insecticide typically depends on the particular target species.

[0263] Beneficial Insect Species The compounds and compositions and combinations of the present invention can be substantially non-toxic to beneficial insect species, including pest predatory and pollinating species.Important pollinating species include bees, such as insects of the superfamily Apoidea, including the Apidae family, such as Bombus, such as Bombus terrestris.Important predatory species include Coccinellidae (ladybird beetles), such as Adalia bipunctata.

[0264] Substantially non-toxic means that the compounds and compositions and combinations of the present invention do not cause the death of beneficial insect species (e.g., pollinator species), and suitably do not cause premature death of beneficial insect species (e.g., pollinator species).This also means that the compounds and compositions and combinations of the present invention do not cause adverse side effects on beneficial insect species (e.g., pollinator species), for example, they do not have a negative effect on feeding behavior or ability to move.

[0265] composition The inventors have provided a composition comprising at least one insecticidal compound of the present invention or a combination thereof that can specifically bind to insects.Importantly, through this interaction with a specific molecular structure of insects, such as a receptor, suitably a neurological receptor, the composition disclosed herein can inhibit, prevent or reduce one or more biological activities of insects, such that the growth or fecundity of insects is inhibited, prevented or reduced.In certain embodiments, the composition disclosed herein can specifically bind to insect receptors and kill insects through the specific interaction of at least one insecticidal compound contained in the composition.

[0266] The composition of the present invention or the composition for use according to the present invention typically comprises a compound as described, in combination with one or more auxiliary components, such as a solvent, a carrier, an excipient, an adjuvant, a preservative, a dispersant, an emulsifier, or a synergist.Suitably, the composition may be an agricultural composition, an insect control composition (e.g., an insecticide composition), or a plant protection composition.

[0267] In any of these embodiments, the compound of the invention or the combination of compounds of the invention may be provided as part of a composition, such as an agricultural composition, an insect control composition (e.g., an insecticide composition) or a plant protection composition. Thus, any reference herein to the application or use of a compound or combination should be interpreted as including the application or use of the appropriate composition, unless the context requires otherwise.

[0268] The compositions typically include a compound described herein in admixture with one or more auxiliary components, such as a solvent, carrier, excipient, adjuvant, preservative, dispersing agent, emulsifier, or synergist.

[0269] The compositions may further comprise combinations of one or more additional active pesticides as described herein.

[0270] The present invention further includes compositions, such as agricultural compositions, insect control compositions or plant protection compositions, comprising the compounds of the present invention, or combinations thereof, mixed with one or more solvents, carriers, excipients, adjuvants, preservatives, dispersants, emulsifiers or synergists. The compositions may be aqueous compositions, further details of which are described herein below.

[0271] "Agricultural" as used herein means suitable for use in the agricultural or agrochemical industry, including horticulture, floriculture and home and garden uses, for protecting plants or plant parts, crops, bulbs, tubers, fruits (e.g., from harmful organisms, diseases or pests); for controlling and preferably promoting or increasing the growth of plants; and / or for promoting the yield of harvested plants, crops or plant parts (e.g., their fruits, flowers, seeds, etc.), and also means products intended for non-crop related uses, e.g., for use by public health / pest control professionals to control unwanted insects and rodents, for home use, e.g., household fungicides and insecticides and agents. Examples of such substances will be clear to those skilled in the art, and preferably include compounds that are active in the context of the present invention as insecticides (e.g., contact or systemic insecticides, including insecticides for home use). Other such agricultural chemicals may be pesticides, growth regulators, nutrients / fertilizers, repellents, defoliants, etc.

[0272] "Agricultural use", as used herein, includes not only the use of the pesticidal compounds of the present invention, combinations or compositions thereof, and optionally agricultural chemicals as defined above (e.g. pesticides, growth regulators, nutrients / fertilizers, repellents, defoliants, etc.) suitable and / or intended for use in field-grown crops (e.g. agriculture), but also the use of the compounds of the present invention, combinations or compositions thereof, and said agricultural chemicals as defined above, suitable and / or intended for use in greenhouse-grown crops (e.g. horticulture / floriculture) or hydroponics systems, as well as the use of the compounds of the present invention, combinations or compositions thereof, and agricultural chemicals as defined above, suitable and / or intended for non-crop use, such as use in a personal garden, for home use (e.g. herbicides or insecticides for home use), or for use by pest control professionals (e.g. weed control, etc.).

[0273] Suitably, the insect control composition according to the present invention is for controlling insect populations. The formulation of such compositions for controlling insect populations is known to those skilled in the art, and includes, but is not limited to, liquid emulsifiable concentrates, wettable powders, solutions, suspension concentrates, emulsions, suspoemulsions, granules and water-dispersible granules (Non-Patent Document 3). Preferably, the insect control composition according to the present invention comprises the combination of the insecticidal compound of the present invention and, optionally, further insecticidal compounds. Suitably, the insecticidal compound is contained in a carrier as described herein below.

[0274] The compositions of the present invention may include pesticide formulations or agrochemical formulations. "Pesticide formulation" as used herein means any composition containing a compound or combination of compounds intended to prevent, destroy, repel, attract or suppress any pest. "Agrochemical formulation" as used herein means a composition for agricultural use containing a biologically active agent, optionally with one or more additives that support optimal dispersion, atomization, distribution, retention and / or activity of the agrochemical. As non-limiting examples, such additives are excipients, solvents, adjuvants, surfactants, wetting agents, spreading agents, oils, sticking agents, penetrating agents, buffers, oxidizing agents, defoamers or drift control agents.

[0275] Composition, as used herein, refers to a composition comprising at least one active substance, suitably the insecticidal compound of the present invention, optionally with one or more additives that support optimal dispersion, atomization, deposition, leaf wetting, distribution, retention and / or uptake of said active substance. Composition, as used herein, includes biological insect control agent or biological insecticide, and it will become clear from the further description herein that these terms are used interchangeably in this application. Thus, composition, as used herein, includes a composition comprising at least one biological molecule as an active ingredient, substance or element for controlling pests in plants or other agriculturally relevant settings (e.g., in soil). Suitably, wherein the at least one biological molecule comprises the insecticidal compound of the present invention or a combination thereof. Suitably, wherein the pest is an insect. As non-limiting examples, additives in the compositions disclosed herein may include, but are not limited to, excipients, solvents, adjuvants, surfactants, wetting agents, spreading agents, oils, adhesion agents, thickening agents, penetrating agents, buffers, oxidizing agents, anti-settling agents, cryoprotectants, light protection agents, antifoam agents, biocides, and / or drift control agents.

[0276] Suitably, the compositions of the present invention are aqueous compositions.

[0277] The compound content of the composition can vary within wide limits. The compound concentration of the composition is suitably an effective amount, which may be 0.0000001-95% by weight of the compound, preferably 0.0001-1% by weight. The terms "effective amount" and "effective dose" as used herein refer to the amount required to achieve the desired result.

[0278] In certain embodiments, the concentration of the compound of the present invention contained in the composition may be at least 0.0001% by weight. In certain embodiments, the concentration of the compound of the present invention contained in the composition may be up to 50% by weight. In certain embodiments, the concentration of the compound of the present invention contained in the composition may be 0.0001% to 50% by weight. In certain embodiments, the present invention provides a composition comprising at least one insecticidal compound of the present invention, wherein the concentration of the at least one compound of the present invention in the composition ranges from 0.001% to 50% by weight. In yet another specific embodiment, the concentration of the at least one compound of the present invention contained in the composition may be 0.001% to 50% by weight. In yet another specific embodiment, the concentration of the at least one compound of the present invention contained in the composition may be 0.01% to 50% by weight. In yet another specific embodiment, the concentration of the at least one compound of the present invention contained in the composition may be 0.1% to 50% by weight.

[0279] The composition of the present invention, or the composition for use according to the present invention, may comprise a combination of more than one compound of the present invention, and / or a combination of other insecticidal compounds as described herein. Thus, the composition of the present invention may, for example, comprise a first compound of the present invention and a second compound of the present invention, or a first compound of the present invention and a second insecticidal compound. Suitably, the first and second compounds may be any of those described herein and may be present in the composition in any relative ratio.

[0280] The composition may be an aqueous composition, for example a saline composition. The aqueous composition may contain one or more buffers, for example, phosphate buffer (for example, phosphate buffered saline) or Tris buffer. Alternatively, the composition may be an oil dispersion or emulsion, for example, an emulsion of oil and water. Alternatively, the composition may be, for example, a suspension, a powder, a foam, a paste, a granule, an aerosol, impregnated natural and synthetic materials, or encapsulated in a polymeric material. The appropriate form of the composition may be selected for the intended use, taking into account the target insect and its habitat.

[0281] Adjuvants may enhance product performance by, for example, increasing the efficiency of delivery of the active ingredient, reducing the level of active ingredient required, or extending the range of effectiveness.

[0282] Different types of adjuvants provide various benefits and advantages, which are achieved by adjusting properties such as spread formation, spread retention, wetting, deposit formation, or uptake.

[0283] Adjuvants that control spray formation can impact spray quality by reducing spray drift and wastage, allowing more of the product to reach the target. This can reduce use rates, resulting in a better environmental profile and a potentially more cost-effective solution. Such adjuvants include non-ionic surfactants and emulsifier blends.

[0284] Adjuvants that control spray retention can dissipate the kinetic energy of the droplets during impact, meaning there is less chance of rebounding or spilling. Such adjuvants include alkyl polyglucosides, alkoxylated alcohols, and polyoxyethylene monobranched alcohols (e.g., polyoxyethylene (8) monobranched alcohol).

[0285] Adjuvants that modify wetting properties (i.e., wetting agents) can reduce surface tension and contact angles, resulting in enhanced coverage. Such adjuvants include polyoxyethylene sorbitan monolaurate (e.g., polyoxyethylene (8) sorbitan monolaurate), surfactant blends, and alkyl polyglucosides.

[0286] Adjuvants that control deposit formation can affect the evaporation of water from the droplets, thus achieving a more uniform distribution. Such adjuvants include alkoxylated polyol esters, polyoxyethylene sorbitan monolaurate (e.g., polyoxyethylene (12) sorbitan monolaurate), and alkyl polyglucosides.

[0287] Adjuvants that modulate uptake can improve the penetration and uptake of active ingredients, for example through insect cuticles, resulting in increased bioavailability. Such adjuvants include alkoxylated polyol esters and polyoxyethylene sorbitan monolaurate (e.g., polyoxyethylene (12) sorbitan monolaurate and polyoxyethylene (16) sorbitan monolaurate).

[0288] Dispersants can be aqueous or non-aqueous. Oil-based dispersant (OD) formulations typically contain solid active ingredients dispersed in oil. The oil can vary from paraffinic to aromatic solvent types and vegetable oils or methylated seed oils. Typically, the active ingredients are uniformly suspended in the oil phase. Although primarily used for water-sensitive active ingredients, OD formulations have been extended to other active ingredients due to their better spray retention, spreadability, foliar uptake, and enhanced penetration (e.g., across insect cuticles) since the carrier oil often acts as an adjuvant.

[0289] Suitable oils for use in the OD dispersion include linseed, rapeseed and soybean oil.

[0290] Aqueous dispersions may be used, for example, to improve stability in the spray tank after dilution in water, and can include modified styrene acrylic polymers, and polymeric amphoteric dispersants and adjuvants.

[0291] When the OD formulation is diluted before application, an emulsifier can be used to emulsify the continuous oil phase into water. Emulsifiers can be selected based on their ability to spontaneously form emulsions. Their performance is primarily influenced by the nature of the surfactants and their aggregation effects on how they behave themselves at the oil / water interface. Examples include polyoxyethylene sorbitol hexaoleate (e.g., polyoxyethylene (40) sorbitol hexaoleate), emulsifier blends, and calcium alkylarylsulfonate.

[0292] The composition may further comprise an adhesive or a dye.

[0293] The compounds may be provided in the form of a concentrate for dilution prior to application. Alternatively, the compounds may be provided in a solid form that is suspended or dissolved prior to formulation.

[0294] The compositions disclosed herein are themselves in a wide variety of solid or liquid forms. As solid composition forms, mention may be made of dispersible powders (content of active substance that may be up to 100%) and granules, in particular those obtained by extrusion, by compaction, by impregnation of granulated carriers, by granulation using powders as starting material (the content of active substance in these granules is 0.5-80% for these latter cases). Such solid compositions may optionally be used in the form of more or less viscous liquids, depending on the type of application desired, such as by dilution in water. As liquid composition forms, or forms intended to constitute a liquid composition during application, mention may be made of solutions, in particular water-soluble concentrates, emulsions, suspension concentrates, wettable powders (or dispersible powders), oils and waxes. Suspension concentrates which can be applied by spraying are prepared so as to obtain stable, flowable products which do not form deposits; these usually contain 10-75% of active substance, 0.5-15% of surfactants, 0.1-10% of thixotropic agents, 0-10% of suitable additives such as antifoams, corrosion inhibitors, stabilizers, penetrating agents and adhesives, and, as carrier, water or an organic liquid in which the active substance is not soluble or only poorly soluble: some organic solids or inorganic salts may be dissolved in the carrier to help prevent settling or may be dissolved as antigels for the water.

[0295] "Carrier", as used herein, means any solid, semi-solid or liquid carrier in or on which an active substance, e.g., a pesticidal compound or combination of the present invention, can be suitably incorporated, contained, immobilized, adsorbed, absorbed, bound, encapsulated, embedded, attached or contained. Non-limiting examples of such carriers include nanocapsules, microcapsules, nanospheres, microspheres, nanoparticles, microparticles, liposomes, vesicles, beads, gels, weak ionic resin particles, liposomes, cochleate delivery vehicles, small granules, particulates, nanotubes, buckyballs, water droplets that are part of a water-in-oil emulsion, oil droplets that are part of an oil-in-water emulsion, organic materials such as cork, wood or other plant derived materials (e.g., in the form of seed husks, wood chips, pulp, spheres, beads, sheets or any other suitable form), paper or cardboard, inorganic materials such as talc, clay, microcrystalline cellulose, silica, alumina, silicates and zeolites, or microbial cells (e.g., yeast cells) or suitable fractions or fragments thereof.

[0296] In one embodiment, the carrier is a liposome. In one embodiment, the composition of the invention suitably further comprises one liposome, wherein each liposome comprises a compound of the invention, or a combination thereof. Suitably, therefore, the invention provides a composition or formulation comprising a plurality of liposomes, said liposomes comprising a compound of the invention, or a combination thereof. Suitably, the liposome comprises lipid components, which may suitably be soy lecithin and glycerol. Suitably, the liposome is formed with soy lecithin and glycerol. Suitably, the liposome is formed with 25 mg / ml glycerol and 3% glycerol. Suitably, the liposome comprises an effective concentration of the compound of the invention. Suitably, the liposome comprises approximately 10 -4M, a compound of the invention, or a combination thereof. Suitably therefore the invention provides a composition or formulation comprising a plurality of liposomes, said liposomes comprising a compound of the invention, or a combination thereof, soy lecithin (preferably 25 mg / ml) and glycerol (preferably 3%).

[0297] Suitably, the liposomes may be prepared by the Mozafari heating method ((Non-Patent Document 4)). Suitably, such a method comprises: (a) mixing the compound of the invention with glycerol, suitably a 50% glycerol solution; (b) mixing the mixture of step (a) with soybean lecithin, suitably 350 mg soybean lecithin in an aqueous solution; (c) heating the mixture of step (b) with stirring at approximately 60° C. and approximately 800 RPM for approximately 40 minutes to form liposomes; (d) slowly cooling the liposomes, suitably by placing them in water at 40° C. for approximately 1-2 hours; and (e) sonicating the liposomes in a sonication bath, suitably for approximately 30 minutes.

[0298] Suitably, the liposomes have an average diameter of approximately 150-250 nm, suitably approximately 175 nm-225 nm, suitably approximately 190 nm-210 nm, suitably approximately 200 nm. Suitably, the size of the liposomes is determined using dynamic light scattering (DLS), for example by using a Malvern Zetasizer Nano. Suitably, the liposomes have a polydispersity index of 0.25-0.35, suitably 0.26-0.33, suitably 0.26-0.31, suitably 0.26-0.30, suitably 0.26-0.29, suitably 0.26-0.28, suitably approximately 0.26.

[0299] In the compositions of the present invention, the carrier with one or more pesticidal compounds may be maintained, for example, as a wettable powder, a wettable powder granule, an emulsifiable concentrate, a suspension concentrate, a microemulsion, a capsule suspension, a dry microcapsule, a tablet or a gel, or may be suspended, dispersed, emulsified or otherwise incorporated in a suitable liquid medium (e.g., water or another suitable aqueous, organic or oily medium) to provide a (concentrated) liquid composition of the present invention having a stability that allows the composition of the present invention to be suitably stored or (after further dilution, if necessary) applied to the intended site of action. Suitably, the compositions of the present invention may be transported and / or stored prior to end use as a suitable liquid concentrate, dry powder, tablet, capsule suspension, slurry or "wet cake", which may optionally (and usually preferably) be suitably diluted, dispersed, suspended, emulsified or otherwise suitably reconstituted by the end user prior to end use. The compositions of the present invention can be applied to the intended site of action using any suitable or desired manual or mechanical technique, such as spraying, pouring, dripping, brushing, coating, drip coating, application as droplets, mist or aerosol, or any other suitable technique, which in one embodiment is an intact, live insect, and even more preferably, the surface of the insect.

[0300] The composition may be a bait composition for ingestion by a target insect. The bait composition may include one or more feeding stimulants, i.e., substances that induce the insect to ingest the compound. Feeding stimulants may include artificial sweeteners, amino acids, other peptides or proteins, and carbohydrates (e.g., glucose, fructose, sucrose, maltose), etc. Examples include honey, syrup, and aqueous solutions of sucrose.

[0301] Commercially available base formulations may also be suitable for use in formulating the compounds described herein, for example, Armid® FMPC (Akzo Nobel).

[0302] The compositions may contain one or more synergists, i.e., compounds that increase the effectiveness of insecticides against their targets, often by inhibiting the insect's ability to metabolize the active agent. Common synergists include piperonyl butoxide and MGK-264 (n-octylbicycloheptane dicarboximide), or peptidase inhibitors.

[0303] The composition may include one or more agents that promote the stability of the pesticidal compound of the present invention. Suitably, the one or more agents that promote stability may prevent the degradation of the pesticidal compound of the present invention. Suitable agents that prevent the degradation of the pesticidal compound of the present invention may inhibit or reduce the activity of enzymes, suitably enzymes that act to degrade proteins, suitably, for example, proteases. Suitably, therefore, the composition may include one or more protease inhibitors, suitably, selected from Bowman-Birk inhibitors, Kunitz inhibitors, cystatins, trypsin inhibitors, serpins, tannins, proteinase inhibitor-II (PI-II), and Alpha-AI1.

[0304] The composition may further comprise one or more additional attractants, sterilants, acaricides, nematicides, fungicides, growth regulators or herbicides.

[0305] In some embodiments, the composition may contain one or more additional pesticides or agricultural chemicals, such as herbicides (e.g., contact or systemic herbicides, including herbicides for home use), fungicides (e.g., contact or systemic fungicides, including fungicides for home use), nematicides (e.g., contact or systemic nematicides, including nematicides for home use) and other pesticides or biocides (e.g., agents for killing insects or snails); and fertilizers; growth regulators, e.g. For example, they may include plant hormones; micronutrients, safeners, pheromones; repellents; insect baits; and / or active agents known per se for this purpose, such as nucleic acids (e.g. single- or double-stranded RNA used in the context of RNAi technology) and other factors, proteins, chemicals, etc., which are used to modulate (i.e. increase, decrease, inhibit, enhance and / or induce) gene expression (and / or other biological or biochemical processes) in or by a targeted plant (e.g. a plant to be protected or controlled).

[0306] Examples of such agricultural chemicals will be apparent to those skilled in the art; for example, but not limited to: glyphosate, paraquat, metolachlor, acetochlor, mesotrione, 2,4-D, atrazine, glufosinate, sulfosate, fenoxaprop, pendimethalin, picloram, trifluralin, bromoxynil, clodinafop, fluroxypyr, nicosulfuron, bensulfuron, imazethapyr, dicamba, imidacloprid, thiamethoxam, fipronil, chlorpyrifos, deltamethrin, lambda-cyhalothrin, endosulfan, methamidophos, carbazole, carbazole-1, carbazole-2, carbazole-3, carbazole-4, carbazole-5, carbazole-6, carbazole-7, carbazole-8, carbazole-9, carbazole-10, carbazole-11, carbazole-12, carbazole-13, carbazole-14, carbazole-15, carbazole-15, carbazole-15, carbazole-16, carbazole-17, carbazole-18, carbazole-19, carbazole-21, carbazole-22, carbazole-23, carbazole-24, carbazole-25, carbazole-25, carbazole-25, carbazole-34, carbazole-35, carbazole-25, carbazole-25, carbazole-35, carbazole-15, carbazole-16, carbazole-25, carbazole-17, carbazole-18, carbazole-25, carbazole-19, carbazole-25, carbazole-34, carbazole-19, carbazole-25, carbazole-19, carbazole-25, carbazole-34, carbazole-1 These include bofuran, clothianidin, cypermethrin, abamectin, diflufenican, spinosad, indoxacarb, bifenthrin, tefluthrin, azoxystrobin, thiamethoxam, tebuconazole, mancozeb, cyazofamid, fluazinam, pyraclostrobin, epoxiconazole, chlorothalonil, copper fungicides, trifloxystrobin, prothioconazole, difenoconazole, carbendazim, propiconazole, thiophanate, sulfur, boscalid, chlorantraniliprole and other known agrochemicals or any suitable combination thereof.

[0307] Methods for Producing Insecticidal Compounds The pesticidal compounds described herein may be produced by any method known in the art for the production of peptides. In one embodiment, the pesticidal compounds may be produced by chemical methods, suitably chemical synthesis methods.

[0308] Any suitable chemical method may be used to synthesize the pesticidal compounds of the present invention.

[0309] Suitably, the insecticidal compounds are peptides. Suitably, they are therefore synthesized by solid-state peptide synthesis. Suitably, such synthesis can be carried out by using commercially available machines, such as the Biotage Initiator+Alstra microwave-assisted peptide synthesizer or the CEM Liberty Prime microwave-assisted peptide synthesizer.

[0310] In one embodiment of the invention, the insecticidal compound is a peptide of formula: [Pyr]-AIMARPQVPRL-[NH2] (SEQ ID NO: 2). Suitably, this peptide may be synthesised by the method defined in the Examples. Suitably, by the method defined in Figure 2.

[0311] In a further aspect of the invention there is provided an isolated pesticidal compound produced by the process of the invention.Suitably an isolated pesticidal compound of formula (I) produced by the process of the invention.

[0312] In a further aspect of the present invention, there is provided a method of producing a composition disclosed herein comprising at least the steps of: (a) obtaining at least one pesticidal compound of formula (I); and (b) formulating the pesticidal compound into a composition.

[0313] In a further aspect of the present invention, there is provided a method for generating and / or producing variants of the insecticidal compound of formula (I), which may comprise the steps of (i) modifying peptide Z of formula (I) by adding, substituting or deleting at least one amino acid; and (ii) assessing the variant thus produced for its insecticidal activity and, optionally, for at least one property selected from the group consisting of biostability, chemical stability, bioavailability, solubility (including the ability to form a stable formulation), producibility and production costs. If the insecticidal activity is reduced compared to unmodified peptide Z, repeating the process of steps (i) and (ii) until a variant with improved insecticidal activity is obtained. If the insecticidal activity is improved compared to unmodified peptide Z, the method may comprise the further steps of producing, isolating and purifying the variant. Screening for insecticidal activity and other above mentioned properties may be carried out as described below or is generally known to the skilled person.

[0314] In one embodiment, a) modifying peptide Z by adding, substituting or deleting at least one amino acid; b) assessing the performance of the variant with respect to its insecticidal activity, and optionally at least one property selected from the group consisting of biostability, chemical stability, bioavailability, solubility (including the ability to form a stable formulation), producibility, and production costs; c) if the insecticidal activity is reduced compared to the insecticidal compound containing unmodified peptide Z, repeating the process of steps (a) and (b) until a variant having improved insecticidal activity is obtained; d) further producing, isolating and purifying the mutant if the insecticidal activity is improved compared to the insecticidal compound containing the unmodified peptide Z. The present invention provides a method for producing a mutant of the insecticidal compound of the present invention, comprising:

[0315] Suitably, the step of obtaining at least one pesticidal compound comprises (a) chemically synthesising the pesticidal compound.

[0316] Suitable compositions are described herein above.Suitable manufacturing methods for compounding compositions are known in the art, and include but are not limited to high or low shear mixing, wet or dry grinding, drip casting, encapsulation, emulsification, coating, dusting, pilling, extrusion granulation, fluidized bed granulation, coextrusion, spray drying, spray chilling, atomization, addition or condensation polymerization, interfacial polymerization, in situ polymerization, coacervation, spray encapsulation, cooling melt dispersion, solvent evaporation, phase separation, solvent extraction, sol-gel polymerization, fluidized bed coating, pan coating, melting, passive or active absorption or adsorption.

[0317] The features disclosed in the above description, or in the following claims, or in the accompanying drawings, whether expressed in their specific form, or in terms of means for performing a disclosed function, or a method or process for obtaining a disclosed result, may, where appropriate, be utilized separately or in any combination of such features to realise the invention in diverse forms thereof.

[0318] While the present invention has been described in conjunction with the exemplary embodiments set forth above, many equivalent modifications and variations will be apparent to those skilled in the art when presented with this disclosure. Accordingly, the exemplary embodiments of the present invention set forth above are considered to be illustrative and not limiting. Various modifications to the described embodiments may be made without departing from the spirit and scope of the present invention.

[0319] For the avoidance of doubt, the theoretical explanations provided herein are provided for the purpose of improving the understanding of the reader, and the inventors do not wish to be bound by any of these theoretical explanations.

[0320] The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

[0321] Aspects and embodiments of the present invention will now be discussed with reference to the accompanying figures. [Brief description of the drawings]

[0322] [Figure 1] The chemical structure of SB-P-47 is shown; [Diagram 2] Showing the chemical synthesis route for synthesizing SB-P-47; [Diagram 3] Shown is an HPLC trace of SB-P-47; [Figure 4] Shown is the LC-MS trace of SB-P-47; [Diagram 5] Leaf dip assay experimental setup shown; [Figure 6] Showing activity data for unformulated SB-P-47 against green peach aphid (Myzus persicae) after 120 hours; [Figure 7] Showing activity data for unformulated SB-P-47 against green peach aphid (Myzus persicae) over time; [Figure 8]Shows activity data for unformulated SB-P-47 (top graph) or NSB48-encapsulated SB-P-47 (bottom graph) at 1x10-4M against Rhopalosiphum padi over time; [Figure 9] Honeybee oral toxicity results expressed as % survival 96 hours after application of SB-P-47 are shown; [Figure 10] PGRO field trials (Wigtoft site) showing reduction in numbers of black bean aphids (Aphis fabae) from unformulated SB-P-47 application as a percentage of untreated control crops (vine beans) counted 4 days following application; [Figure 11] PGRO field trial (Holbeach site) showing reduction in black bean aphid (Aphis fabae) numbers from unformulated SB-P-47 application as a percentage of untreated control crop (vine beans) counted 7 days following application; [Figure 12] AgriScience field trials (Greece) are shown as a percentage of an untreated control crop (cotton) counted 3 days following application. The data show a reduction in cotton aphid (Aphis gossypii) numbers from unformulated SB-P-47 application; [Figure 13] Particle size of liposome suspensions with and without SB-P-47 is shown; [Figure 14] 1 shows activity data for unformulated SB-P-47 against naturally infested black bean aphids (Aphis fabae) in a field trial conducted by PGRO 4 days after application and 8 days after application. [Figure 15] Further data from the AgriScience field trial (Greece) is shown in Figure 12. The data show the reduction in numbers of green peach aphid (M. persicae) from unformulated SB-P-47 application at 1 x 10-4 M as a percentage of an untreated control crop (cotton) counted 3 to 21 days following application. Two applications (7 days apart) were made; [Figure 16]Further AgriScience field trials (Greece) are shown. Data show reduction in numbers of green peach aphid (M. persicae) from unformulated SB-P-47 application at 1 x 10-4 M as a percentage of untreated control crop (melon) counted 2-14 days following application. Two applications (7 days apart) were made; [Figure 17] ResAgraria field trial (Italy). Data shows reduction in lettuce long-horn aphid (Nasonovia ribisnigri) numbers from unformulated SB-P-47 application at 1×10-4 M as a percentage of an untreated control crop (lettuce) counted 2-10 days following application A, and 2, 7, and 10 days after application B. Two applications (7 days apart) were made; [Figure 18] ResAgraria field trial (Italy). Data shows reduction in numbers of green peach aphid (M. persicae) from unformulated SB-P-47 application at 1 x 10-4 M as a percentage of an untreated control crop (cucumber) counted 2 to 21 days following application. Two applications (7 days apart) were made; [Figure 19] Demonstrating the field stability of SB-P-47 over time; [Figure 20] Showing the stability of SB-P-47 under UV lamp over time; [Figure 21] 1 shows the aqueous stability of SB-P-47 at 54° C. over time. EXAMPLES

[0323] The present invention is illustrated and further described by the following non-limiting examples.

[0324] General Procedure All amino acids are of the L configuration unless otherwise stated. Standard Fmoc-protected amino acids were purchased from CEM Corporation or Pepceuticals. Specialist amino acid suppliers are indicated, as well as peptide synthesis resin suppliers, when appropriate. Peptide grade DMF was purchased from Rathburn.

[0325] Peptides were synthesized on a Biotage Initiator+Alstra microwave assisted peptide synthesizer or a CEM Liberty Prime microwave assisted peptide synthesizer as specified.

[0326] High resolution mass spectrometry (HRMS) was performed on a Bruker microTOF-Q II (ESI+).

[0327] Peptides were purified on a reversed-phase Dionex HPLC system equipped with a Dionex P680 pump and a Dionex UVD170U UV-vis detector (monitoring at 214 nm and 280 nm) using a Phenomenex, Gemini, C18, 5 μm, 250 × 21.2 mm column. A gradient was run using solvents consisting of A (HO + 0.1% TFA) and B (MeCN + 0.1% TFA) and fractions were lyophilized on a Christ Alpha2-4LO plus lyophilizer.

[0328] Pure peptides were analyzed on a Shimadzu reversed-phase HPLC (RP-HPLC) system equipped with a Shimadzu LC-20AT pump, a SIL-20A autosampler and an SPD-20A UV-vis detector (monitoring at 214 nm and 280 nm) using a Phenomenex, Aeris, 5 μm, peptide XB-C18, 150 × 4.6 mm column at a flow rate of 1 mL / min. The RP-HPLC gradient was performed using a solvent system consisting of solutions A (100% HO + 0.1% TFA) and B (100% MeCN + 0.1% TFA). Typically, two gradients were used to characterize each peptide; a gradient of 5% to 95% solution B over 20 min (incorporating a 2 min hold at 5% solution B and a 5 min wash with 95% solution B at the beginning and end of the gradient, respectively), and a gradient of 5 to 95% solution B over 50 min (incorporating a 5 min hold at 5% solution B and a 5 min wash with 95% solution B at the beginning and end of the gradient, respectively). In some cases, specialized gradients were used and this is indicated where appropriate. Analytical RP-HPLC data are reported as column retention time (tR) in minutes (min). The analytical column was maintained at ambient temperature.

[0329] LC-MS analysis was performed on a Thermo Scientific LCQ Fleet quadrupole mass spectrometer with an m / z range of 50-2000 Da with an ESI source coupled to a Dionex Ultimate3000LC. The analysis was performed on a ReprosilGold120C18, 3 μm, 150×4 mm column using a linear gradient from buffer A (95 / 5 H2O / MeCN with 0.1% v / v TFA) to buffer B (95 / 5 MeCN / H2O with 0.1% v / v TFA) over 20 min (incorporating a 2 min hold at 0% solution B and a 5 min wash with 100% solution B at the beginning and end of the gradient, respectively). Similar LC-MS gradients were used when compounds were characterized using specialized analytical RP-HPLC gradients. Analytical RP-HPLC and LC-MS samples were injected as 25 μL stocks with a concentration of 1 mg / mL in HO / MeCN with 0.1% v / v TFA. The LC-MS column oven temperature was maintained at 30 °C.

[0330] High resolution mass spectrometry (HRMS) of the pure peptides was performed on a Bruker microTOF-Q II (ESI+).

[0331] Proton nuclear magnetic resonance spectroscopy ( 1 H NMR was recorded on an AVANCE III400 Bruker (400 MHz). Proton chemical shifts are expressed in parts per million (ppm, σ scale) and are referenced to residual protium in the NMR solvent (CDCl3, d7.26; CD3OD, d3.31 and DO, d4.79). Where appropriate, the following abbreviations were used to describe peak patterns: br=broadened, s=singlet, d=doublet, t=triplet, q=quartet, m=multiplet. Coupling constants J are reported in Hertz (Hz).

[0332] General Procedure for Automated Peptide Synthesis Biotage Initiator + Alstra synthesis machine: Fmoc-protected amino acids were prepared as 0.2M (0.1mmol synthesis), 0.5M (0.2mmol synthesis) or 0.7M (0.5mmol synthesis) solutions in DMF. Five equivalents of amino acid (relative to resin loading) were used during the coupling cycle. Oxyma and diisopropylcarbodiimide (DIC) were prepared as 0.2M (0.1mmol synthesis), 0.5M (0.2mmol synthesis) or 0.7M (0.5mmol synthesis) solutions in DMF. Five equivalents of Oxyma and five equivalents of DIC (relative to resin loading) were used during the coupling cycle. For Fmoc deprotection, a solution of 20% morpholine in DMF (with 5% formic acid) was used. Coupling reactions were carried out under microwave heating at 90°C for 2 minutes, except for Fmoc-Cys(Trt)-OH, Fmoc-His(Trt)-OH and Fmoc-Arg(PBf)-OH. Coupling of Fmoc-Cys(Trt) and Fmoc-His(Trt)-OH was carried out for 10 min at 50° C. Coupling of Fmoc-Arg(Pbf)-OH was carried out for 2 min at 90° C. for two consecutive cycles (double coupling). Microwave-assisted Fmoc deprotection was carried out at 90° C. for 1 min.

[0333] CEM Liberty Blue Synthesizer Fmoc-protected amino acids were prepared as 0.2M solutions in NBP (Tamisolve). Five equivalents of amino acid (relative to resin loading) were used during the coupling cycle. Oxyma was prepared as a 0.5M solution in NBP. DIC was prepared as a 5M solution in NBP. Five equivalents of Oxyma and five equivalents of DIC (relative to resin loading) were used during the coupling cycle. For Fmoc deprotection, a solution of 20% pyrrolidine was used. Coupling reactions and Fmoc deprotection were carried out under microwave heating at 90° C. for 2 and 1 min, respectively, except for Fmoc-Cys(Trt)-OH, Fmoc-His(Trt)-OH, and Fmoc-Arg(Pbf)-OH. Coupling of Fmoc-Cys(Trt) and Fmoc-His(Trt)-OH was carried out at 50° C. for 5 min. Coupling of Fmoc-Arg(Pbf)-OH was carried out at 75° C. for two consecutive cycles of 5 min.

[0334] General procedure for TFA cleavage of peptides Typically, peptide cleavage tests were performed by taking approximately 3 mg of dried resin beads and treating them with TFA / TIS / water (95:2.5:2.5) for 3 hours. The filtrate was drained, concentrated, and then triturated in cold diethyl ether (Et2O). The triturate was dissolved in acetonitrile / water and then analyzed by RP-HPLC / LC-MS.

[0335] Peptides were typically cleaved from the bulk resin by gently rocking the resin in a cleavage cocktail of TFA / TIS / HO (95:2.5:2.5) at room temperature for 3 h, then drained and the TFA swept away with a steady stream of N2 gas. Peptides containing cysteine ​​or tryptophan residues were cleaved from the resin for 3 h using a cleavage cocktail of TFA / TIS / HO / DODT (94:2.5:1:2.5). In all cases, the crude peptides were triturated with cold Et2O. The Et2O was removed from the crude peptide pellet thus obtained under a steady stream of nitrogen. The crude peptides were then redissolved in HO / MeCN and purified by RP-HPLC.

[0336] The specific synthetic route for SB-P-47 is shown in Figure 2. For the 0.25 mmol scale synthesis of SB-P-47, a double coupling step was used for 8Gln and a single coupling step of 4 min at 90 °C was used for 6Arg and 11Arg. When the synthesis was performed on 0.5 mmol, a 6 min coupling cycle was performed for 4Met and an extended 7 min Arg coupling cycle was used for 6Arg and 11Arg. A double coupling step was used for Ile3 and Gln8. Instead of the 0.2 M concentration applied for all other Fmoc-AA-OH building blocks, Fmoc-Arg(Pbf)-OH and Boc-Pyr-OH were used at a concentration of 0.12 M and Fmoc-Gln(Trt)-OH and Fmoc-Met-OH were used at a concentration of 0.15 M. Purification was performed at 60° C. with monitoring at 240 nm using a gradient of 10-35% B over 20 min. Purity ≧99%, yield=15%.

[0337] Unless otherwise stated herein, peptides were synthesized according to the general procedures above along with the exemplary procedures below, or directly ordered.

[0338] Mortality Assessment Methodology Leaf dip assay The assay was performed based on IRAC susceptibility testing method 019 ( https: / / irac-online.org / methods / aphids-adultnymphs / ).

[0339] Small 4 cm wide and 3 cm high dishes are filled with 1% agar treatment solution of active chemicals or controls (ensuring a 1 cm gap between the agar and the lid) and allowed to solidify. 2.5 cm leaf pieces are dipped into 3 ml of treatment solution, allowing the treatment to coat the leaf. The leaf pieces are allowed to dry for 1 hour and placed on the solidified agar. An insect (aphid Myzus persicae or Rhopalosiphum padi) is placed on each of the leaf pieces. Each unit is sealed with a tight-fitting, air-permeable lid. The agar dishes are placed in a small plastic tray lined with moist tissue paper, ensuring that the bottom water tray of the incubator is filled with clean water and placed in the incubator. Mortality assessments are made at 72, 96 and 120 hours. The leaf immersion assay set-up is shown in FIG. 5. Leaf dip assays were performed with SB-P-47 and compared to a negative control vehicle and the current commercial insecticide, spirotetramat. The activity of SB-P-47 against the green peach aphid (Myzus persicae) is shown in Figures 6 and 7; SB-P-47 has good activity while being environmentally friendly and targeting specific pests unlike broad spectrum chemical insecticides, e.g., spirotetramat. Leaf dip assays were also performed with encapsulated SB-P-47 against the wheat curl aphid (Rhopalosiphum padi), as shown in Figure 8. The peptides were encapsulated into liposomes as described below.

[0340] Protocol for encapsulation of SB-P-47 in liposomal formulations (NSB48) Mozafari heating method for liposomal preparations. Soy lecithin (350 mg, Thermo Scientific Chemicals) was added to MilliQ water (7 mL) with stirring. -4A final peptide concentration of 100 μM was added to a 6% glycerol solution (7 mL). Both solutions were stirred at room temperature for 1 h. Subsequently, the peptide solution was added to the lipid solution. This solution was heated to 60°C for 40 min in an oil bath with stirring at 800 RPM. Subsequently, the liposomes were placed in a 40°C water bath for 1-2 h and allowed to cool slowly. The sample was then sonicated in a sonicator bath for 30 min (2×15 min) at room temperature.

[0341] [Table 6]

[0342] [Table 7]

[0343] NSB48_C, containing peptide SB-P-47, had a particle diameter of 203 nm and a polydispersity of 0.026. Liposomes containing no peptide had a particle size of 174 nm. The data are shown in FIG.

[0344] Particle size determination Dynamic light scattering (DLS) is the most commonly used technique to assess nanoparticle size. The liposome mixture was used directly as prepared. DLS analysis was performed on a Malvern Zetasizer Nano.

[0345] Honeybee Survival Research A honeybee oral test protocol adapted from OECD Test No. 247: Bumblebee, Acute Oral Toxicity Test, was performed. The toxicity of SB-P-47 was compared to a negative control of sucrose or vehicle, and to the current commercial insecticide imidacloprid. Toxicity data is shown in Figure 9; SB-P-47 has much lower toxicity to important pollinator species, such as honeybees, compared to broad spectrum chemical insecticides, such as imidacloprid.

[0346] Field Testing Field trials were performed to assess the performance of peptide insecticidal candidates in real-world field conditions. The data below was filtered for the purpose of showing peptide efficacy. Data was processed in licensed ARM field trial software.

[0347] PGRO field trial data set Field trials on peptide SB-P-47 have been conducted by PGRO and have shown good results in real world conditions, most notably when the peptide was sprayed onto crops in a laboratory grade solution. PGRO has conducted field trials in the UK and demonstrated highly effective activity of peptide SB-P-47 for aphid control as shown in Figure 10.

[0348] The third PGRO test (slot test), shown in Figure 11, again demonstrated the effectiveness of the peptide, showing that SB-P-47 performed as effectively as the conventional pesticides tested, despite low aphid infestation.

[0349] Further field testing showed that unformulated SB-P-47 performed comparably to Hallmark Zeon insecticide against black bean aphids (Aphis fabae) 4 and 8 days after application, as shown in FIG.

[0350] AgriScience Field Trial Dataset AgriScience conducted field trials in Greece to investigate the efficacy of insecticidal peptides against aphids on cotton crops. The trials observed superior results for the insecticidal activity of SB-P-47 in this cotton trial, but the peptide performed with similar efficacy as conventional pesticides that were also tested, as shown in Figure 12.

[0351] More AgriScience field trial data sets AgriScience conducted field trials in Greece, as described above with respect to FIG. 12, and found that 1×10-4 The effectiveness of the insecticidal peptide SB-P-47 at concentrations of M was investigated and further data is presented here from studies over 3-14 days. As mentioned above, the studies observed excellent results for the insecticidal activity of SB-P-47 in this scenario, as shown in Figure 15.

[0352] Similar trials were also conducted on aphids, M. persicae, on melon crops in Greece over a period of 2-14 days. Again, the trials showed excellent results for the insecticidal activity of SB-P-47, as shown in FIG.

[0353] ResAgraria field trial dataset ResAgraria has conducted two field trials in Italy, demonstrating that 1×10 β-glutamate was effective against lettuce aphid (Nasonovia ribisnigri) on lettuce crops for 2-10 days (Figure 17) and against green peach aphid (Mysuz persicae) on cucumber crops for 2-21 days (Figure 18). -4 We investigated the efficacy of the insecticidal peptide SB-P-47 at a concentration of M. Through testing, we observed superior results for the insecticidal activity of SB-P-47, but the peptide performed with similar efficacy to conventional pesticides that were also tested, as shown in Figures 17 and 18, respectively.

[0354] Stability Testing Protocol Simulate plant growth field stability Peptide stock solutions were prepared as 1 mg / mL in ddH2O in Eppendorf tubes and placed in the plant cabinet. Samples were taken at 48 hours, 72 hours, 1 week and 2 weeks for analysis. For each sample, 250 μL was taken. To this, 5 drops of MeCN+0.1% formic acid were added and the samples were analyzed by LCMS and HPLC. The results are shown in Figure 19.

[0355] UV Drying Lamp Stability Peptide stock solutions were prepared as 1 mg / mL in ddH2O in Eppendorf tubes and placed in a UV drying lamp chamber. The temperature was recorded throughout using a thermometer and found to be stable at 40°C. Samples were taken for analysis at 0, 24, 48 and 72 hours. For each sample, 250 μL was taken. To this, 5 drops of MeCN+0.1% formic acid were added and the samples were analyzed by LCMS and HPLC. The results are shown in Figure 20.

[0356] Stability at 54°C Peptide stock solutions were prepared as 1 mg / mL in ddH2O in Eppendorf tubes and placed in a ThermoBloc set at 54°C. The temperature was recorded throughout using a thermometer. Samples were taken for analysis at 0, 48, 168 and 336 hours. For each sample, 250 μL was taken. To this, 5 drops of MeCN+0.1% formic acid were added and the samples were analyzed by LCMS and HPLC. The results are shown in Figure 21.

[0357] References In order to more fully describe and disclose the present invention and the state of the art to which it pertains, several publications are cited. Full citations for these references are provided below. Each of these references is incorporated herein by reference in its entirety. ·Koyama T,Terhzaz S,Naseem MT,Nagy S,Rewitz K,Dow JAT,Davies SA,Halberg KV.A nutrient-responsiveHormonal circuit mediates an inter-tissue program regulating metabolicHomeostasis in adult Drosophila.Nat Commun.2021 ·Kean L,Cazenave W,Costes L,Broderick KE,Graham S,Pollock VP,Davies SA,Veenstra JA,Dow JA.Two nitridergic peptides are encoded by the gene capability in Drosophila melanogaster.Am J Physiol Regul Integr Comp Physiol.2002 ·Yeoh JGC,Pandit AA,Zandawala M,Naessel DR,Davies SA,Dow JAT.DINeR:Database for Insect Neuropeptide Research.Insect Biochem Mol Biol.017 ·Ahn SJ,Corcoran JA,Vander Meer RK,Choi MY.Identification and Characterization of GPCRs for Pyrokinin and CAPA Peptides in the Brown Marmorated Stink Bug,HalyomorphaHalys-(Hemiptera:Pentatomidae).Front Physiol.2020 ·Audsley N and Down RE,G protein coupled receptors as targets for next generation pesticides.Insect Biochem Molec 67:27-37(2015). ·Halberg KA,Terhzaz S,Cabrero P,Davies SA and Dow JAT,Tracing the evolutionary origins of insect renal function.Nat Commun 6(2015). ·Dow JA,Insights into the Malpighian tubule from functional genomics.J Exp Biol 212:435-445(2009). ·Huesmann GR,Cheung CC,Loi PK,Lee TD,Swiderek KM and Tublitz NJ,Amino acid sequence of CAP2b,an insect cardioacceleratory peptide from the tobaccoHawkmoth Manduca sexta.FEBS Lett 371:311-314(1995). ·Davies SA,Cabrero P,Povsic M,ohnston NR,Terhzaz S and Dow JAT,Signaling by drosophila capa neuropeptides.Gen Comp Endocr 188:60-66(2013). ·Terhzaz S,Teets NM,Cabrero P,Henderson L,Ritchie MG,Nachman RJ,Dow JAT,Denlinger DL and Davies SA,Insect capa neuropeptides impact desiccation and cold tolerance.Proc Natl Acad Sci 201501518(2015). ·Terhzaz S,Alford L,Yeoh JGC,Marley R,Dornan AT,Dow JAT and Davies SA,Renal neuroendocrine control of desiccation and cold tolerance by Drosophila suzukii.Pest Manag Sci 74:800-810(2017). ·Predel R,Wegener C,Biology of the CAPA peptides in insects.Cell Mol Life Sci 63:2477-2490(2006). ·Lamango NS,Nachman RJ,Hayes TK,Strey A and Isaac RE,Hydrolysis of insect neuropeptides by an angiotensin converting enzyme from theHousefly,M.domestica.Peptides 18:47-52(1997). ·Terhzaz S,Cabrero P,Robben JH,Radford JC,Hudson BD,Milligan G,Dow JA and Davies SA,Mechanism and function of Drosophila capa GPCR:a desiccation stress-responsive receptor with functionalHomology toHuman neuromedinU receptor.PLoS One 7(1):e29897(2012). ·Blackman RL and Eastop VF,Aphids on the World’s Crops:An Identification Guide,John Wiley&Sons Ltd,Chichester,UK.(2000). ·Dow JAT,Maddrell SHP,Gortz A,Skaer NJV,Brogan S and Kaiser K,The Malpighian tubules of Drosophila melanogaster-a novel phenotype for studies of fluid secretion and its control.J Exp Biol 197:421-428(1994). ·Davies SA,Huesmann GR,Maddrell SH,O’Donnell MJ,Skaer NJ,Dow JAT and Tublitz NJ,CAP2b,a cardioacceleratory peptide,is present in Drosophila and stimulates tubule fluid secretion via cGMP.Am J Physiol 269:R1321-R1326(1995). ·Beyenbach KW,Skaer H and Dow JA,The developmental,molecular,and transport biology of Malpighian tubules.Annu Rev Entomol 55:351-374(2010). ·Sadeghi A.,an Damme,E.J.M.and Smagghe G.(2009)Evaluation of the susceptibility of the pea aphid,Acyrthosiphon pisum,to a selection of novel biorational insecticides using an artificial diet.Journal of Insect Science 9:65. ·Van Emden F(2009).Artificial diet for aphids-thirty years’experience.REDIA,XCII:163-167 ·Mozafari,M.R.Nanoliposomes:preparation and analysis.Liposomes:Methods and Protocols, Volume 1:Pharmaceutical Nanocarriers (2010):29-50.

Claims

1. The following formula (I): R １ -Y １ -Z-Y ２ -R ２ (I) [In the formula: R １ is hydrogen (which may be represented as "H-" or "Hy-"); １～４ alkyl (e.g., methyl, ethyl, propyl, butyl), formyl, acyl, fatty acyl, sugar moiety, phosphate or sulfate, or R １ is the formula 【Chemistry 1】 is a pyroglutamate group of Alkyl, formyl, acyl or fatty acyl is oxo or C １～６ may be optionally substituted with one or more groups selected from alkyl, or a sugar moiety, phosphate or sulfate; Y １ is absent or a peptide containing 1-2 amino acids; Z is of the formula AIMARPQVPRL (SEQ ID NO: 1) is a peptide according to Y ２ is absent or a peptide containing 1-2 amino acids; R ２ NH ２ , N.R. ２ａ H, N.R. ２ａ R ２ｂ , OH or OR ２ａ where R ２ａ and R ２ｂ Each of, when present, independently represents １～６ -alkyl (e.g. methyl, ethyl, propyl, butyl, pentyl or hexyl). or a salt or solvate thereof.

2. R １ is selected from hydrogen, acyl or fatty acyl, or phosphate or sulfate, or R １ But, the formula 【Chemistry 2】 is a pyroglutamate group of 2. The insecticidal compound of claim 1, wherein the acyl or fatty acyl is optionally substituted with a sugar moiety, a phosphate or a sulfate.

3. R １ is hydrogen, formyl, acetyl (Ac), propanoyl, butanoyl, palmitoyl, butyryl, cerotoyl, decanoyl, docosenoyl, dodecanoyl, eleostearoyl, heptanoyl, hexanoyl, icosanoyl, icosenoyl, lignoceroyl, linoleoyl, lipoyl, myristoleoyl, nonanoyl, octadecanoyl, octanoyl, palmitoleoyl, stearoyl, undecanoyl, valeryl, and the formula: 【Chemistry 3】 is selected from the pyroglutamate group Preferably, R １ is selected from hydrogen, palmitoyl, or pyroglutamate, more preferably R １ 3. The insecticidal compound according to claim 1 or claim 2, wherein is pyroglutamate.

4. Y １ is not present; and / or Y ２ is present and selected from GR, RG, KR, RK, K, R, and G; and / or R ２ But NH ２ The insecticidal compound according to any one of claims 1 to 3,

5. formula: [Pyr]-AIMARPQVPRL-[NH ２ ] (SEQ ID NO: 2) 2. The insecticidal compound of claim 1 having the formula:

6. A composition comprising a compound according to any one of claims 1 to 5, mixed with one or more solvents, carriers, excipients, adjuvants, preservatives, dispersants, emulsifiers or synergists, optionally an aqueous composition, preferably comprising an effective amount of said compound.

7. The composition according to claim 6, which is an agricultural composition, preferably an insect control composition or a plant protection composition.

8. Use of a compound according to any one of claims 1 to 5 or a composition according to claim 6 or 7 as an insect control agent or as a plant protection agent for protecting plants or parts thereof against insects.

9. a) a dipteran insect (preferably, said dipteran insect is selected from D. melanogaster or D. suzukii); b) Hemiptera, such as aphids (preferably, the Hemiptera are selected from Aphis fabae, Aphis gossypii, Acyrthosiphon pisum, Myzus persicae, Rhopalosiphum padi, or Nasonovia ribisnigri); and / or c) lepidopteran insects (preferably, said lepidopteran insects are selected from the diamondback moth (Plutella xylostella); d) cockroach insects; and / or e) Coleoptera Use of a compound or composition according to claim 8 against 9. Use of the compounds according to claim 8, preferably against the peach aphid (Myzus persicae) insect.

10. 10. A method for increasing insect mortality comprising contacting an insect or a population of insects with a compound according to any one of claims 1 to 5, or a composition according to claim 6 or 7.

11. 10. A method for inhibiting or preventing infestation of a plant by an insect, comprising contacting the plant or a part thereof, or a site on which the plant is growing or intended to grow, with a compound according to any one of claims 1 to 5, or a composition according to claim 6 or 7.

12. 12. The method of claim 11, wherein the compound or composition is contacted with the plant or part thereof, or with a site where the plant is growing or intended to grow, while the plant or part is free or substantially free of insects.

13. 10. A method of reducing or treating insect infestation of a plant or reducing the insect load on a plant, comprising contacting the plant or a part thereof, or a site on which the plant is growing, with a compound according to any one of claims 1 to 5, or a composition according to claim 6 or 7.

14. 13. The method of claim 11 or 12, wherein the site on which the plant is growing or intended to grow may comprise an agricultural site suitable for growing plants, preferably the site comprises a farm field.

15. The insect is a) a dipteran insect (preferably, said dipteran insect is selected from D. melanogaster or D. suzukii); b) Hemiptera, such as aphids (preferably, the Hemiptera are selected from Aphis fabae, Aphis gossypii, Acyrthosiphon pisum, Myzus persicae, Rhopalosiphum padi, or Nasonovia ribisnigri); c) lepidopteran insects (preferably, said lepidopteran insects are selected from the diamondback moth (Plutella xylostella); d) cockroach insects; and / or e) Coleoptera and The method according to any of claims 10 to 14, wherein the insect is preferably a Myzus persicae insect.

16. 16. The method of any of claims 10 to 15, wherein contacting the insect or insect population, plant or part thereof, or site comprises watering, feeding, spraying, atomizing, foaming, fogging, cultivating in hydroculture, cultivating in hydroponics, coating, submerging, injecting and / or dusting the insect or insect population, plant or part thereof, or site with the compound or composition.

17. The insect or insect population, plant or part thereof, or site is treated with an effective concentration of the compound, preferably 10 －３ ~10 －９ The method according to any one of claims 10 to 16, wherein the contact is carried out at a concentration of M.

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