Insect neuropeptide analogues

Abstract

The present invention relates to bifunctional insect neuropeptide compounds and analogues thereof, having activity against insects, for example hemipteran, dipteran, lepidopteran, blattodea and / or coleopteran insects, such as aphids and fruit flies, and their use as insect control agents (e.g. insecticides) and plant protection agents.

Description

INSECT NEUROPEPTIDE ANALOGUES Field of the Invention

[0001] The present invention relates to bifunctional insect neuropeptide compounds and analogues thereof, having activity against insects, for example hemipteran, dipteran, lepidopteran, blattodea and / or coleopteran insects, such as aphids and fruit flies, and their use as insect control agents (e.g. insecticides) and plant protection agents. Background

[0002] With a global dependence on broad-spectrum insecticides, the damaging effects of which are well documented, there is increasing need for the development of greener, target- specific insecticides with which to protect valuable crop plants. The development and employment of neuropeptides, and their synthetic analogues offers a promising avenue in the drive for greener and target-specific insecticidal agents.

[0003] Within insects, neuropeptides are regulatory peptides with functional roles in growth and development, behaviour and reproduction, metabolism and homeostasis, and muscle movement. Insect neuropeptide families are large and include the insect kinins and CAPA (CAPA, CAP2b, CAPA3) neuropeptides, AKH peptides, and the pyrokinin peptides.

[0004] Due to their high specificity, insect neuropeptides and their cognate receptors (G- protein coupled receptors, GPCRs) may be developed towards insecticidal agents to selectively reduce the fitness of target pest insects, whilst minimising detrimental environmental impacts, and minimising harm to other non-target species such as pollinators, which have seen dangerously declining population numbers due to pesticide / insecticide use.

[0005] AKH is known to modulate lipid homeostasis Gäde G, Auerswald LGen Comp Endocrinol.2003 Jun 1;132(1):10-20. doi: 10.1016 / s0016-6480(03)00159-x.

[0006] The present invention provides adipokinetic hormone (AKH) peptides and analogues. Summary of the Invention

[0007] The inventors have discovered new peptides capable of binding to both AKH and kinin receptors. The peptides therefore have insecticidal activity against insects that encode AKH peptides and / or also insects that encode kinin peptides. Particular insects include lepidopteran insects, and so the peptides potentially find use as pest control agents or insecticides, while having little or no effect against important pollinator species such as bees.

[0008] The peptides of the present invention are preferably therefore capable of binding to both AKH and kinin receptors.

[0009] Thus, in a first aspect, the invention provides a peptide compound having the formula (I) below:R1-X-Y-Z-R2(I) wherein: R1is hydrogen (which may be designated "H-" or "Hy-"), C1-4alkyl (e.g. methyl, ethyl, propyl, butyl), formyl, or pyroglutamate; X is absent or is selected from Q#or E#; Y is a peptide moiety of the formula: Y1- Y2- F#-Y4wherein: Y1is L#, I#or V#; Y2is T#or S#; Y4is absent or is T#; Z is a peptide moiety of the formula: Z1-Z2-Z3-W#-Z5-Z6wherein: Z1is absent or is selected from F#, T#or Y#; Z2is selected from S#, Y#, K#, N# or H#; Z3is selected from S#, A#, P#, V# or T#; Z5is selected from G#, A#; Z6is absent or is G#; wherein “ ” indicates that the residue is independently the listed unmodified amino acid, a modified amino acid or a non-natural amino acid analogue; and R2is NH2, NR2aH or NR2aR2b; wherein each of R2aand R2bif present are independently C1-6-alkyl (e.g. methyl, ethyl, propyl, butyl, pentyl or hexyl); wherein if X is Q#or E#, then R1is not pyroglutamate.

[0010] In preferred embodiments of the invention, the peptide is a bifunctional peptide compound capable of binding to both AKH and kinin receptors.

[0011] In certain embodiments, the compounds of Formula (I) comprise at least one modified amino acid or non-natural amino acid analogue, e.g. in the X, Y and / or Z group. The at least one modified amino acid or non-natural amino acid analogue may be as defined anywhere herein.

[0012] The label “#” indicates that the residue in question may be a modified version of the listed amino acid, or that the reside may be replaced by a non-natural amino acid analogue. For example, S#, indicates that the reside may be serine, a modified serine (e.g. D-serine, beta-serine etc.) or a non-natural amino acid (e.g. [Aib]).

[0013] In another aspect, there is provided a composition comprising a compound as defined herein, or a salt or solvate thereof, in admixture with one or more solvents, carriers, diluents, adjuvants, preservatives, dispersants, emulsifying agents, or synergists. Suitably, the composition is an agricultural composition, an insect control composition or plant protection composition.

[0014] In another aspect, there is provided the use of a compound as defined herein, or a salt or solvate thereof, or a composition as defined herein, as an insect control agent. The use may be as an insecticide against insects that encode an AKH and / or a kinin peptide. The use may be as an insecticide against hemipteran, dipteran, lepidopteran, blattodea and / or coleopteran insects, preferably lepidopteran insects.

[0015] In another aspect, there is provided a method of increasing insect mortality, the method comprising contacting an insect population with a compound as defined herein, or a salt or solvate thereof, or a composition as defined herein. Suitably, the insect is an insect that encodes an AKH peptide and / or a kinin, such as hemipteran, dipteran, lepidopteran, blattodea and / or coleopteran insects, preferably lepidopteran insects.

[0016] In another aspect, there is provided a method of increasing hemipteran, dipteran, lepidopteran, blattodea and / or coleopteran insect mortality, the method comprising contacting a hemipteran, dipteran, lepidopteran, blattodea and / or coleopteran insect population with a compound as defined herein, or a salt thereof, or a composition as defined herein.

[0017] In another aspect, there is provided the use of a compound as defined herein, or a salt or solvate thereof, or a composition as defined herein, as a plant protection agent, for protecting a plant against insects that encode an AKH and / or a kinin peptide.

[0018] In another aspect, there is provided the use of a compound as defined herein, or a salt or solvate thereof, or a composition as defined herein, as a plant protection agent, for protecting a plant against hemipteran, dipteran, lepidopteran, blattodea and / or coleopteran insects, preferably lepidopteran insects.

[0019] In another aspect, there is provided a method of inhibiting infestation of a plant by insects that encode an AKH and / or a kinin peptide, the method comprising contacting the plant with a compound as defined herein, or a salt or solvate 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 that encode an AKH and / or a kinin peptide.

[0020] In another aspect, there is provided a method of inhibiting infestation of a plant byhemipteran, dipteran and / or lepidopteran 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 hemipteran, dipteran, lepidopteran, blattodea and / or coleopteran insects. Preferably the insects are selected from hemipteran, dipteran and / or lepidopteran insects.

[0021] In another aspect, there is provided a method of reducing infestation of a plant by insects that encode an AKH and / or a kinin peptide, or of reducing load of insects that encode an AKH and / or a kinin peptide on a plant, the method comprising contacting the plant with a compound as defined herein, or a salt or solvate thereof, or a composition as defined herein.

[0022] In another aspect, there is provided a method of reducing hemipteran, dipteran, lepidopteran, blattodea and / or coleopteran insect infestation of a plant, or of reducing hemipteran, dipteran, lepidopteran, blattodea and / or coleopteran insect load 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.

[0023] Suitable insects which encode the AKH and / or a kinin peptide include hemipteran, dipteran, lepidopteran, blattodea and / or coleopteran insects, preferably lepidopteran insects.

[0024] In another aspect, there is provided a method of producing an insecticidal compound according to the first aspect, the method comprising: (a) chemically synthesising the compound of formula (I), or a precursor thereof.

[0025] In one embodiment, the chemical synthesis comprises the method described in the examples.

[0026] In another aspect there is provided the use of a compound or a composition as defined herein as an insect control agent, or as a plant protection agent for protecting a plant or part thereof against insects.

[0027] In another aspect there is provided the use of a compound or a composition as defined herein against: a) dipteran insects, preferably wherein the dipteran insects are selected from: D. melanogaster or D. suzukii; b) hemipteran insects, such as aphids, preferably wherein the hemipteran insects are selected from: Aphis fabae, Acyrthosiphon pisum, Myzus persicae, Amrasca biguttula or Rhopalosiphum padi; and / or c) lepidopteran insects, preferably wherein the lepidopteran insects are selected from: Plutella xylostella or Spodoptera frugiperda; and / or d) blattodea insects, preferably wherein the blattodea insects are Blattella germanica.

[0028] In a preferred embodiment, there is provided the use of a compound or a composition as defined herein against lepidopteran insects, preferably wherein the lepidopteran insects are selected from: Plutella xylostella or Spodoptera frugiperda.

[0029] In another aspect there is provided a method of increasing insect mortality, the method comprising contacting an insect or insect population with a compound or a composition as defined herein.

[0030] In another aspect there is provided a method of inhibiting or preventing infestation of a plant by insects, the method comprising contacting the plant or a part thereof, or a site on which the plant is growing or is intended to be grown, with a compound or a composition as defined herein. Suitably, the compound or composition is contacted with the plant or part thereof, or a site on which the plant is growing or is intended to be grown, while the plant or part is free or substantially free of insects.

[0031] In another aspect there is provided a method of reducing or treating an insect infestation of a plant, or of reducing insect load on a plant, the method comprising contacting the plant or a part thereof, or a site on which the plant is growing, with a compound or a composition as defined herein.

[0032] Suitably, the site on which the plant is growing or intended to be grown may comprise an agricultural site suitable for growing plants, preferably the site comprises a field.

[0033] Suitably, the insects are: a) dipteran insects, preferably wherein the dipteran insects are selected from: D. melanogaster or D. suzukii; b) hemipteran insects, such as aphids, preferably wherein the hemipteran insects are selected from Aphis fabae, Acyrthsiphon pisum, Myzus persicae or Rhopalosiphum padi; c) lepidopteran insects, preferably wherein the lepidopteran insects are selected from: Plutella xylostella or Spodoptera frugiperda; d) coleopteran insects; and / or d) blattodea insects, preferably wherein the blattodea insects are Blattella germanica).

[0034] More suitably, the insects are lepidopteran insects, preferably wherein the lepidopteran insects are selected from: Plutella xylostella or Spodoptera frugiperda.

[0035] Suitably, contacting the insect or insect population, plant or part thereof, or site, comprises watering feeding, spraying, atomizing, foaming, fogging, culturing in hydroculture, culturing in hydroponics, coating, submerging, injecting and / or encrusting the insect or insect population, plant or part thereof, or site with the composition as defined herein. Contactingmay comprise injecting a plant (e.g. a tree) or part thereof with the composition as defined herein, using systems and methods such as those described in WO2020 / 021041, WO2023 / 161802, WO2022 / 264053, WO2022 / 189386, WO2022 / 165248, WO2021 / 152093, WO2020 / 212612 and WO2020 / 021041, the entire contents of which being incorporated by reference.

[0036] Suitably, the insect or insect population, plant or part thereof, or site, is contacted with an effective concentration of the compound as defined herein, preferably a concentration of between 10-3to 10-9M.

[0037] In another aspect, there is provided a method of producing a bifunctional insect neuropeptide, said method comprising the steps of: a. selecting a naturally occurring AKH peptide; and b. modifying the C-terminal region of the naturally occurring AKH so that it comprises a kinin motif.

[0038] Suitably, kinin motif has a formula Z-R2, wherein Z and R2are as defined anywhere herein.

[0039] Suitably, the C-terminal region of the naturally occurring AKH peptide comprises the 4 to 6 amino acids at the C-terminal of the AKH peptide.

[0040] Suitably, the bifunctional insect neuropeptide formed in the above described method is a compound according to formula (I) as defined herein.

[0041] Further features of the aspects and embodiments of the invention will now be defined under the following headed sections. Any feature in any section may be combine with any aspect of embodiment in any workable combination. DETAILED DESCRIPTION OF THE INVENTION Definitions

[0042] It will be understood that references to a “compound of the invention” or “a compound as defined herein” refer to a bifunctional peptide compound according to Formula (I) as described herein.

[0043] Throughout the present description and claims the conventional three-letter and one- letter codes for naturally occurring amino acids are used, i.e. 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).

[0044] Generally, herein if the one letter code is accompanied by a “#” symbol, it indicates that it may be either in its naturally occurring form, a modified form, or may be replaced with a non-proteinogenic amino acid. For Example, “A#” encompasses unmodified alanine, a modified alanine (e.g. N-methyl alanine) or indicates that an alanine residue could be replaced by another non-natural amino acid analogue (e.g. α-aminoisobutyric acid (Aib)).Suitably, for example in the residues may be in a naturally occurring form or a modified form. Suitably, a single residue in a peptide may be replaced with a non-proteinogenic amino acid.

[0045] ‘Amino acid’ as referred to herein may refer to a naturally occurring amino acid or any other amino acid including synthetic amino acids, and non-proteinogenic amino acids. By “naturally occurring” in this context is meant the 20 amino acids encoded by the standard genetic code, sometimes referred to as proteinogenic amino acids.

[0046] The term amino acid is short for α-amino [alpha-amino] carboxylic acid. Each molecule contains a central carbon (C) atom, called the α-carbon, to which both an amino and a carboxyl group are attached. The remaining two bonds of the α-carbon atom are generally satisfied by a hydrogen (H) atom and the side chain, shown as R below:

[0047] The modified amino acid in the present invention may be an α-alkylated amino acid, in which the α hydrogen atom has been replaced with a C1-6alkyl group, e.g. a methyl or an ethyl group. Preferably, the α alkylated amino acid is an α-methylated amino acid, e.g. α- methyl-L-serine (given the notation [α-Me)S]):α-methyl-L-serine

[0048] Generally accepted three-letter codes and other abbreviations for other amino acids may also be employed, such as hydroxyproline (Hyp: L-hydroxyproline or (2S,4R)-4- Hydroxyproline), Octahydroindole-2-carboxylic acid (Oic), sarcosine (Sar), norleucine (Nle), α-aminoisobutyric acid (Aib), naphthylalanine (Nal), thiazolidine-4-carboxylic acid (Thz), phenylglycine (Phg) etc.

[0049] The term “Nal” indicates that an amino acid residue has been replaced with a naphthylalanine residue:.

[0050] The term “Thz” indicates that an amino acid residue has been replaced with a thiazolidine-4-carboxylic acid residue, for example (R)-thiazolidine-4-carboxylic acid:(R)-thiazolidine-4-carboxylic acid.

[0051] Ahx indicates 6-aminohexanoic acid (also known as 6-aminocaproic acid or ε- aminocaproic acid). Ado indicates 12-aminododecanoic acid.

[0052] The notation "n-me" before an amino acid code is used to indicate an N-methylated amino acid residue. Thus, for example, "[n-me-V]" indicates N-methyl valine, "[n-me-A]" indicates N-methyl alanine and "[n-me-L]" indicates N-methyl leucine.

[0053] The notation ‘tBu’ after an amino acid code is used to indicated a tertiary butyl modified amino acid residue. Thus, for example “Ser(tBu)” indicates tert-butyl serine.

[0054] The notation ‘Boc’ after an amino acid code is used to indicate an amino acid residue modified with a tert-butyloxycarbonyl protecting group.

[0055] The residue sarcosine ([Sar]) is alternative name for an N-methyl glycine ([n-me-G]) residue:.

[0056] Such other amino acids may be shown in square brackets “[ ]” (e.g. “[Aib]”) when used in a general formula or sequence in the present specification, especially when the rest of the formula or sequence is shown using the single letter code.

[0057] Unless otherwise specified, amino acid residues in peptides of the invention are ofthe L-configuration. However, D-configuration amino acids may be incorporated as modifications. In the present context, an amino acid code written with a small letter may be used to represent the D-configuration of said amino acid, e.g. [a] represents the D- configuration of alanine.

[0058] Residues of beta amino acids may also be employed in compounds the invention. Such residues may be designated by a "β'' symbol followed by the conventional code for the corresponding alpha amino acid. Thus, [βhL] (or [B3L]) represents a residue of beta- homoleucine (3-amino-5-methylcaproic acid), [βA] represents a residue of beta-alanine (3- aminopropanoic acid), [βhA] (or [B3A]) represents a residue of beta-homoalanine, [βhV] represents a residue of beta-homovaline, sometimes referred to as beta-leucine (3-amino-4- methylpentanoic acid), [βhF] (or [B3F]) represents a residue of beta-homo-phenylalanine, [βhP] (or [B3P]) represents a residue of beta-homoproline.

[0059] A “peptoid analogue” of an amino acid is an analogue in which the side chain is connected to the nitrogen of the peptide backbone, instead of the α-carbon as in proteinogenic peptides. Such residues may be designated by a "Peptoid'' notation followed by the conventional code for the corresponding alpha amino acid. An example of a peptoid includes a peptoid of phenylalanine:A peptoid of phenylalanine. The above residue may also have the notation [Peptoid-F], [Peptoid-Phe] or [NPhe], indicating a peptoid of phenylalanine.

[0060] A “biotin modified” amino acid analogue is an amino acid residue which incorporates a biotin moiety as part of the side chain. For example, the notation “[Biotin-K]” indicates a lysine residue modified at the side chain to include a biotin moiety:The biotin moiety may also be attached to the amino acid side chain via a linker group, e.g. a PEG or amino-terminated PEG group. For example, an aspartic acid (or glutamine) side chain modified with a PEG-linked biotin moiety:(the above residue is given the notation [Biotin-PEG-D])

[0061] Alternatively, or in addition, a biotin moiety may be at a terminal position. Thus, R1 may be biotin. The notation [Biotin]- represents a terminal biotin moiety, for example a partial sequence [Biotin]-S has the formula:

[0062] The modification of the amino acids may involve the side chains of two particularamino acids being covalently linked, e.g. via an intramolecular reaction between the side chains, resulting in a cyclic amide structure in the peptide sequence. Such a structure may be formed by intramolecular amide formation via condensation reaction between the side chains certain amino acid residues, particularly the side chains of arginine or lysine, and the side chains of aspartic acid or glutamic acid. Suitably, the residues which are linked via an intramolecular side chain reaction are adjacent to one another, spaced one residue apart, or spaced two residues apart.

[0063] A particular example of residues being intramolecularly linked via their side chains (K) and glutamic acid (E), which can undergo amide formation via a condensation reaction. In a particular example, the lysine and glutamic acid are separated by one amino acid residue, for example leucine, as shown below:[cyclic-KLE] Such a group may have the notation [cyclic-KLE], with the bold text indicating that the K and the E residues are linked via their side chains to form a cyclic amide structure.

[0064] As used herein, the terms “polypeptide”, “protein”, “peptide”, are used interchangeably, and refer to a polymeric form of amino acids of any length, which can include coded and non-coded amino acids. As used herein, amino acid residues will be indicated as above either by their full name or according to the standard three-letter or one- letter amino acid code.

[0065] The notation Cx-xx refers to the number of carbon atoms in a functional group. The number in the ‘x’ positions is the lowest number of carbon atoms and the number in the ‘xx’ position denotes the highest number of carbon atoms. For example, C1-6-alkyl refers to alkyl groups as defined herein having from 1 to 6 carbon atoms.

[0066] The notation i, n or t are used herein in relation to various alkyl groups in the normal way. Specifically, the suffixes refer to the arrangement of atoms and denote straight chain (‘n’) or branched (‘i’ or ‘t’) alkyl groups.

[0067] The term “alkyl” as used herein refers to a saturated linear or branched-chain monovalent hydrocarbon radical, wherein the alkyl radical may be optionally substituted. The number of carbon atoms in the alkyl group may be specified using the above notation,for example, when there are from 1 to 8 carbon atoms the term “C1-8-alkyl” may be used. 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).

[0068] An “alkylene,” “alkenylene,” or “alkynylene” group is an alkyl, alkenyl, or alkynyl group that is positioned between and serves to connect two other chemical groups. Thus, “C1-6alkylene” means a linear saturated divalent hydrocarbon radical of one to six carbon atoms or a branched saturated divalent hydrocarbon radical of three to six carbon atoms. Example alkylene groups include methylene (-CH2-), 1,1-ethylene (-CH(CH3)-), 1,2-ethylene (- CH2CH2-), 1,1-propylene (-CH(CH2CH3)-), and 2,2-propylene (-C(CH3)2-).

[0069] The term “alkenyl” as used herein refers to a linear or branched-chain monovalent hydrocarbon radical with at least one site of unsaturation, i.e., a carbon-carbon double bond. The alkenyl radical may be optionally substituted, and includes radicals having "cis" and "trans" orientations, or alternatively, "E" and "Z" orientations. The number of carbon atoms in the alkenyl group may be specified using the above notation, for example, when there are from 2 to 8 carbon atoms the term “C2-8-alkenyl” may be used. Example alkenyl groups include, but are not limited to, ethenyl (-CH=CH2), and prop-1-enyl (-CH=CHCH3).

[0070] In the chemical structures drawn herein, the presence of “” denotes apoint of attachment or a radical for example, a radical as discussed in relation to various functional groups.

[0071] The term “aryl” means a cyclic or polycyclic aromatic ring having from 5 to 12 carbon atoms. The term aryl includes both monovalent species and divalent species. Aryl includes groups having a single ring and groups having more than one ring such a fused rings or spirocycles. In the case of groups having more than one ring, at least one of the rings is aromatic. The number of carbon atoms in the aryl group may be specified using the above notation, for example, when there are from 6 to 16 carbon atoms the term “C6-16-aryl” may be used. Aryl groups may be optionally substituted. Examples of aryl groups include phenyl, naphthyl, biphenyl, phenanthrenyl, naphthacenyl, 1,2,3,4-tetrahydronaphthalenyl, 1H- indenyl, 2,3-dihydro-1H-indenyl, and fluorenyl. A preferred aryl group is fluorenyl.

[0072] The term “heteroaryl” or “heteroaromatic” means an aromatic mono-, bi-, or polycyclic ring incorporating one or more (for example 1-4, particularly 1, 2 or 3) heteroatoms selected from nitrogen, oxygen or sulfur. The term heteroaryl includes both monovalent species and divalent species. Examples of heteroaryl groups are monocyclic and bicyclic groups containing from five to twelve ring members, and more usually from five to ten ring members. The heteroaryl group can be, for example, a 5- or 6-membered monocyclic ring or a 9- or 10- membered bicyclic ring, for example a bicyclic structure formed from fused five and sixmembered rings or two fused six membered rings. Each ring may contain up to about four heteroatoms typically selected from nitrogen, sulfur and oxygen. Typically the heteroaryl ring will contain up to 3 heteroatoms, more usually up to 2, for example a single heteroatom. In one embodiment, the heteroaryl ring contains at least one ring nitrogen atom. The nitrogen atoms in the heteroaryl rings can be basic, as in the case of an imidazole or pyridine, or essentially non-basic as in the case of an indole or pyrrole nitrogen. In general the number of basic nitrogen atoms present in the heteroaryl group, including any amino group substituents of the ring, will be less than five.

[0073] Examples of heteroaryl include furyl, pyrrolyl, thienyl, oxazolyl, isoxazolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, 1,3,5-triazenyl, benzofuranyl, indolyl, isoindolyl, benzothienyl, benzoxazolyl, benzimidazolyl, benzothiazolyl, benzothiazolyl, indazolyl, purinyl, benzofurazanyl, quinolyl, isoquinolyl, quinazolinyl, quinoxalinyl, cinnolinyl, pteridinyl, naphthyridinyl, carbazolyl, phenazinyl, benzisoquinolinyl, pyridopyrazinyl, thieno[2,3-b]furanyl, 2H-furo[3,2-b]-pyranyl, 5H-pyrido[2,3-d]-o-oxazinyl, 1H-pyrazolo[4,3-d]-oxazolyl, 4H-imidazo[4,5-d]thiazolyl, pyrazino[2,3-d]pyridazinyl, imidazo[2,1-b]thiazolyl, imidazo[1,2-b][1,2,4]triazinyl. “Heteroaryl” also covers partially aromatic bi- or polycyclic ring systems wherein at least one ring is an aromatic ring and one or more of the other ring(s) is a non-aromatic, saturated or partially saturated ring, provided at least one ring contains one or more heteroatoms selected from nitrogen, oxygen or sulfur. Examples of partially aromatic heteroaryl groups include for example, tetrahydroisoquinolinyl, tetrahydroquinolinyl, 2-oxo-1,2,3,4-tetrahydroquinolinyl, dihydrobenzthienyl, dihydrobenzfuranyl, 2,3-dihydro-benzo[1,4]dioxinyl, benzo[1,3]dioxolyl, 2,2-dioxo-1,3-dihydro-2-benzothienyl, 4,5,6,7-tetrahydrobenzofuranyl, indolinyl, 1,2,3,4-tetrahydro-1,8-naphthyridinyl, 1,2,3,4-tetrahydropyrido[2,3-b]pyrazinyl and 3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazinyl. A particularly preferred heteroaryl is indolyl, which may be joined to the peptide via a CH2C(O) linker, and designated “[Ind]”.

[0074] Examples of five membered heteroaryl groups include but are not limited to pyrrolyl, furanyl, thienyl, imidazolyl, furazanyl, oxazolyl, oxadiazolyl, oxatriazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, triazolyl and tetrazolyl groups.

[0075] Examples of six membered heteroaryl groups include but are not limited to pyridyl, pyrazinyl, pyridazinyl, pyrimidinyl and triazinyl.

[0076] A bicyclic heteroaryl group may be, for example, a group selected from: a benzene ring fused to a 5- or 6-membered ring containing 1, 2 or 3 ring heteroatoms; a pyridine ring fused to a 5- or 6-membered ring containing 1, 2 or 3 ring heteroatoms;a pyrimidine ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms; a pyrrole ring fused to a 5- or 6-membered ring containing 1, 2 or 3 ring heteroatoms; a pyrazole ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms; a pyrazine ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms; an imidazole ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms; an oxazole ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms; an isoxazole ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms; a thiazole ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms; an isothiazole ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms; a thiophene ring fused to a 5- or 6-membered ring containing 1, 2 or 3 ring heteroatoms; a furan ring fused to a 5- or 6-membered ring containing 1, 2 or 3 ring heteroatoms; a cyclohexyl ring fused to a 5- or 6-membered heteroaromatic ring containing 1, 2 or 3 ring heteroatoms; and a cyclopentyl ring fused to a 5- or 6-membered heteroaromatic ring containing 1, 2 or 3 ring heteroatoms.

[0077] Particular examples of bicyclic heteroaryl groups containing a six membered ring fused to a five membered ring include but are not limited to benzfuranyl, benzthiophenyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzthiazolyl, benzisothiazolyl, isobenzofuranyl, indolyl, isoindolyl, indolizinyl, indolinyl, isoindolinyl, purinyl (e.g., adeninyl, guaninyl), indazolyl, benzodioxolyl and pyrazolopyridinyl groups. A preferred bicyclic heteroaryl group is indolyl.

[0078] Particular examples of bicyclic heteroaryl groups containing two fused six membered rings include but are not limited to quinolinyl, isoquinolinyl, chromanyl, thiochromanyl, chromenyl, isochromenyl, chromanyl, isochromanyl, benzodioxanyl, quinolizinyl, benzoxazinyl, benzodiazinyl, pyridopyridinyl, quinoxalinyl, quinazolinyl, cinnolinyl, phthalazinyl, naphthyridinyl and pteridinyl groups.

[0079] The term halogen as used herein refers the one or more of fluorine (F), chlorine (Cl), bromine (Br) or iodine (I). The term “halo” or “halogeno” refers to fluoro, chloro, bromo and iodo.

[0080] The term “haloalkyl” refers to an alkyl group having on or more halogen substituent. The number of carbon atoms in the haloalkyl group may be specified using the above notation, for example, when there are from 1 to 8 carbon atoms the term “C1-8-haloalkyl” maybe used. Examples of haloalkyl groups include trifluoromethyl (-CF3).

[0081] The term “comprising” is used in the present description and claims, it 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.

[0082] The term “about” as used herein when referring to a measurable value such as a parameter, an amount, a temporal duration, and the like, is meant to encompass variations of + / -10% or less, preferably + / -5% or less, more preferably + / - 1% or less, and still more preferably + / - 0.1% or less of and from the specified value, insofar such variations are appropriate to perform in the disclosed invention. It is to be understood that the value to which the modifier 'about' refers is itself also specifically, and preferably, disclosed.

[0083] “Plant” as used herein, means an entire plant or a part thereof, including fresh fruit, vegetables and seeds. The plant or plant part may be a live plant or part thereof. Also, the term “plant” as used herein encompasses whole plants, ancestors and progeny of the plants and plant parts, including seeds, shoots, stems, leaves, roots (including tubers), flowers, and tissues and organs, wherein each of the aforementioned comprise 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 wherein each of the aforementioned comprises the gene / nucleic acid of interest.

[0084] “Crop” as used herein means a plant species or variety that is grown to be harvested as food, livestock fodder, fuel raw material, or for any other economic purpose. As a non- limiting example, said crops can be maize, cereals, such as wheat, rye, barley and oats, sorghum, rice, sugar beet and fodder beet, fruit, such as pome fruit (e.g. apples and pears), citrus fruit (e.g. oranges, lemons, limes, grapefruit, or mandarins), stone fruit (e. g. peaches, nectarines or plums), nuts (e.g. almonds or walnuts), soft fruit (e.g. cherries, strawberries, blackberries or raspberries), the plantain family or grapevines, leguminous crops, such as beans, lentils, peas and soya, oil crops, such as sunflower, safflower, rapeseed, canola, castor or olives, cucurbits, such as cucumbers, melons or pumpkins, fibre plants, such as cotton, flax or hemp, fuel crops, such as sugarcane, miscanthus or switchgrass, vegetables, such as potatoes, tomatoes, peppers, lettuce, spinach, onions, carrots, egg-plants, asparagus or cabbage, ornamentals, such as flowers (e.g. petunias, pelargoniums, roses, tulips, lilies, or chrysanthemums), shrubs, broadleaved trees (e.g. poplars or willows) and evergreens (e.g. conifers), grasses, such as lawn, turf or forage grass or other useful plants, such as coffee, tea, tobacco, hops, pepper, rubber or latex plants.

[0085] A “pest”, as used here, is an organism that is harmful to plants, animals, humans or human concerns, and includes, but is not limited to crop pests such as insects (as later defined), household pests or insects, such as cockroaches, ants, etc., and disease vectors,such as malaria mosquitoes.

[0086] “Pest infection” or “pest disease” as used herein refers to any inflammatory condition, disease or disorder in a living organism, such as a plant, animal or human, which is caused by a pest.

[0087] “Active substance”, “active ingredient” or “active principle”, as used interchangeably herein, means any biological, biochemical or chemical element and its derivatives, fragments or compounds based thereon, including micro-organisms, having general or specific action against harmful organisms on a subject, and in particular on insect pests of plants, parts of plants or on plant products, as they occur naturally or by manufacture, including any impurity inevitably resulting from the manufacturing process.

[0088] The terms “effective amount” and “effective dose”, as used herein, mean the amount needed to achieve the desired result or results.

[0089] An “insect”, as used here, is used in the broad popular sense and includes all species of the superphylum Panarthropoda (classification Systema Naturae, Brands, S.J. (comp.) 1989- 2005. Systema Naturae 2000. Amsterdam, The Netherlands, [http: / / sn2000.taxonomy.nl / ]), including the phyla Arthropoda, Tardigrada and Onychophora; it includes all the different phases of the life cycle, such as, but not limited to eggs, larvae, nymphs, pupae and adults. Suitable insect pests are defined elsewhere herein.

[0090] An “insecticidal compound” as used herein refers to compounds having biological activity on insects (as defined above), including but not limited to compounds capable of killing the insect, larvaecides, insect growth regulators, behaviour modifying compounds, attractants, repellents, pheromones, kairomones, allomones and entomopathogenic fungi, viruses and proteins. The insecticide exerts its biological activity preferably by the contact of the compound with the insect, without the need of being ingested by the insect. It includes not only compounds or compound formulations that are ready to use, but also precursors in an inactive form, which may be activated by outside factors. Possibly, the insecticide may be combined with materials used in conjunction, such as synergists or safeners, flavour or odour compositions. Preferably, said compound is comprised in a carrier as defined above. “Comprised in a carrier” as used herein means bound on or contained in by means such as but not limited to embedding, encapsulation and adsorption.

[0091] Throughout this specification, including the claims which follow, unless the context requires otherwise, the word “comprise” and “include”, and variations such as “comprises”, “comprising”, and “including” will be understood to imply 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.

[0092] It must 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 dictatesotherwise. 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 the use of the antecedent “about,” it will be understood that the particular value forms another embodiment. The term “about” in relation to a numerical value is optional and means for example + / - 10%. Compounds of The Invention

[0093] Particular compounds of the invention include, for example, compounds of the formula (I), wherein, unless otherwise stated, each of R1, X, Y, Z, R2and any associated substituent group has any of the meanings defined hereinbefore or in any of paragraphs (1) to (43) hereinafter:-(4) Y1is L. (5) Y2is T#. (6) Y2is T. (7) Y4is absent or T. (8) Y4is absent. (9) Z1is absent or is selected from F#or Y#. (10) Z1is absent or is selected from F,Y or [Thi]. (11) Z2is S#. (12) Z2is S or [n-me-S]. (13) Z3is S#. (14) Z3is S or [s] (d-serine). (15) Z5is G#. (16) Z5is G. (17) Z6is absent or G. (18) Z6is absent. (19) X is absent or is selected from Q or E. (20) X is absent. (21) R1is hydrogen or pyroglutamate; (22) R1is pyroglutamate. (23) X is absent and R1is pyroglutamate; or X is selected from Q#or E#and R1is hydrogen.(24) X is absent and R1is pyroglutamate; or X is selected from Q or E and R1is hydrogen. (25) X is absent and R1is pyroglutamate. (26) R2is NH2, NR2aH or NR2aR2b; wherein each of R2aand R2bare independently selected from methyl or ethyl. (27) R2is NH2or NMe2. (28) R2is NH2. (29) Y is a peptide moiety of the formula (Y1): L#-T#-F#-Y4(Y1) wherein Y4as defined anywherein herein; and whereinindicates that the residue is independently the listed unmodified amino acid, a modified amino acid or a non-natural amino acid analogue. (30) Y is a peptide moiety of the formula (Y1a) or (Y1b): L#-T#-F#-T#(Y1a) (SEQ ID NO: 1) L#-T#-F#(Y1b) wherein indicates that the residue is independently the listed unmodified amino acid, a modified amino acid or a non-natural amino acid analogue. (31) Y is a peptide moiety selected from: L-T-F-T (SEQ ID NO: 2); or L-T-F. (32) Z is a peptide moiety of the formula (Z1): Z1-S#-S#-W#-G#-Z6(Z1) (SEQ ID NO: 3) wherein Z1and Z6are as defined anywhere herein; and whereinindicates that the residue is independently the listed unmodified amino acid, a modified amino acid or a non-natural amino acid analogue. (33) Z is a peptide moiety with a formula selected from (Z1a), (Z1b), (Z1c), (Z1d) or (Z1e): S#-S#-W#-G#-G#(Z1a) (SEQ ID NO: 4)S#-S#-W#-G#(Z1b) (SEQ ID NO: 5) F#-S#-S#-W#-G#-G#(Z1c) (SEQ ID NO: 6) F#-S#-S#-W#-G#(Z1d) (SEQ ID NO: 7) Y#-S#-S#-W#-G#(Z1e) (SEQ ID NO: 8) wherein “ ” indicates that the residue is independently the listed unmodified amino acid, a modified amino acid or a non-natural amino acid analogue. (34) Z is a peptide moiety with a formula selected from (Z2a), (Z2b), (Z2c), (Z2d) or (Z2e): S#-S#-W#-G-G (Z2a) (SEQ ID NO: 9) S#-S#-W#-G (Z2b) (SEQ ID NO: 10) F#-S#-W#-G-G (Z2c) (SEQ ID NO : 11) F#-S#-S#-W#-G (Z2d) (SEQ ID NO: 12) Y#-S#-S#-W#-G (Z2e) (SEQ ID NO: 13) wherein “ ” indicates that the residue is independently the listed unmodified amino acid, a modified amino acid or a non-natural amino acid analogue. (35) Z is a peptide moiety with a formula selected from (Z3a), (Z3b), (Z3c), (Z3d) or (Z3e): S#-S-W-G-G (Z3a) (SEQ ID NO: 14) S#-S-W-G (Z3b) (SEQ ID NO: 15) F#-S-W-G-G (Z3c) (SEQ ID NO: 16) F#-S-S-W-G (Z3d) (SEQ ID NO: 17) Y#-S-S-W-G (Z3e) (SEQ ID NO: 18) wherein “ ” indicates that the residue is independently the listed unmodified amino acid, a modified amino acid or a non-natural amino acid analogue. (36) Z is a peptide moiety selected from: [n-me-S]S[Nal]GG (SEQ ID NO: 19); [n-me-S][s][Nal]GG (SEQ ID NO: 52); S-S-W-G-G (SEQ ID NO: 20);S-S-W-G (SEQ ID NO: 21); F-S-S-W-G-G (SEQ ID NO: 22); F-S-S-W-G (SEQ ID NO: 23); Y-S-S-W-G (SEQ ID NO: 24); [Thi]-S-S-W-G (SEQ ID NO: 25). (37) R2is NH2, NR2aH or NR2aR2b, wherein each of R2aand R2bif present is independently selected from C1-2-alkyl. (38) R2 is NH2. (39) Any modified amino acid or non-natural amino acid analogue residues present in peptides X, Y and / or Z are independently selected from: i. an N-methylated amino acid; i. a non-proteinogenic amino acid, e.g. hydroxyproline (Hyp: L- hydroxyproline or (2S,4R)-4-Hydroxyproline), Octahydroindole-2- carboxylic acid (Oic), sarcosine (Sar), norleucine (Nle), α- aminoisobutyric acid (Aib), thienyl alanine (Thi) or thiazolidine-4- carboxylic acid (Thz), phenylglycine (Phg), gamma aminobutyric acid (gaba) or naphthylalanine (Nal); ii. a D-amino acid iii. a beta-amino acid iv. a peptoid amino acid analogue; v. a sugar modified amino acid; or vi. a biotin modified amino acid; or the side chains of two amino acid residues may be joined together to form a cyclic structure (e.g. intramolecular amide formation via condensation reaction between the side chains of arginine or lysine, with the side chain of aspartic acid or glutamic acid). (40) Any modified amino acid or non-natural amino acid analogue residues present in peptides X, Y and / or Z are independently selected from: i. an N-methylated amino acid; ii. a peptoid amino acid analogue; iii. a non-proteinogenic amino acid, selected from hydroxyproline (Hyp: L- hydroxyproline or (2S,4R)-4-Hydroxyproline), Octahydroindole-2-carboxylic acid (Oic), sarcosine (Sar), norleucine (Nle), α- aminoisobutyric acid (Aib), thienyl alanine (Thi), thiazolidine-4- carboxylic acid (Thz) or naphthylalanine (Nal); iv. a D-amino acid; or the side chains of either arginine or lysine, may be joined to the side chain of one of aspartic acid or glutamic acid to form a cyclic amide; preferably wherein the arginine or lysine residue is either adjacent to, or spaced one or two amino acids residues apart from, the aspartic acid or glutamic acid residue, e.g. [cyclic-KXE], wherein “X” is any amino acid residue:wherein R is an amino acid side chain. (41) Any modified amino acid or non-natural amino acid analogue residues present in peptides X, Y and / or Z are independently selected from: i. an N-methylated amino acid; ii. a peptoid amino acid analogue; iii. a non-proteinogenic amino acid, selected from hydroxyproline (Hyp: L- hydroxyproline or (2S,4R)-4-Hydroxyproline), Octahydroindole-2- carboxylic acid (Oic), sarcosine (Sar), norleucine (Nle), α- aminoisobutyric acid (Aib), thienyl alanine (Thi), thiazolidine-4- carboxylic acid (Thz) or naphthylalanine (Nal); iv. a D-amino acid. (42) Any modified amino acid or non-natural amino acid analogue residues present in peptides X, Y and / or Z are independently selected from: i. an N-methylated amino acid; ii. thienyl alanine (Thi); iii. thiazolidine-4-carboxylic acid (Thz)iv. naphthylalanine (Nal); or v. a D-amino acid. (43) Any modified amino acid or non-natural amino acid analogue residues present in peptides X, Y and / or Z is thienyl alanine (Thi).

[0094] Suitably, Y1is as defined in any one of paragraphs (1) to (4) above. More suitably, Y1is as defined in paragraph (3) or (4) above. Most suitably, Y1is as defined in paragraph (4) above.

[0095] Suitably, Y2is as defined in paragraph (5) or (6) above. Most suitably, Y2is as defined in paragraph (6) above.

[0096] Suitably, Y4is as defined in paragraph (7) or (8) above. Most suitably, Y4is as defined in paragraph (8) above.

[0097] Suitably, Z1is as defined in paragraph (9) or (10) above. Most suitably, Z1is as defined in paragraph (10) above.

[0098] Suitably, Z2is as defined in paragraph (11) or (12) above. More suitably, Z2is as defined in paragraph (12) above.

[0099] Suitably, Z3is as defined in paragraph (13) or (14) above. More suitably, Z2is as defined in paragraph (14) above.

[0100] Suitably, Z5is as defined in paragraph (15) or (16) above. More suitably, Z5is as defined in paragraph (16) above.

[0101] Suitably, Z6is as defined in paragraph (17) or (18) above. More suitably, Z6is as defined in paragraph (18) above.

[0102] Suitably, X is as defined in paragraph (19) or (20) above. More suitably, X is as defined in paragraph (20) above.

[0103] Suitably, R1is as defined in paragraph (21) or (22) above. Most suitably, R1is as defined in paragraph (22) above.

[0104] Suitably, X and R1are as defined in any one of paragraphs (23) to (25) above. More suitably, X and R1are as defined in paragraph (24) or (25) above. Most suitably, X and R1are as defined in paragraph (25) above.

[0105] Suitably, Y is as defined in paragraph (29), (30) or (31). More suitably, Y is as defined in paragraph (30) or (31). Most suitably, Y is as defined in paragraph (31).

[0106] Suitably, Z is as defined in any one of paragraphs (32) to (36). More suitably, Z is as defined in any one of paragraphs (34) to (36). Most suitably, Z is as defined in paragraph (36).

[0107] Suitably, R2is as defined in paragraph (37) or (38) above. Most suitably, R2is as defined in paragraph (38) above.

[0108] In certain embodiments, the peptide X-Y-Z comprises 0, 1, 2, 3 or 4 modified amino acids or non-natural amino acid analogues. In certain embodiments, the peptide X-Y- Z comprises 0, 1, 2 or 3 modified amino acids or non-natural amino acid analogues. In certain embodiments, the peptide X-Y-Z comprises 1 or 2 modified amino acids or non- natural amino acid analogues. In certain embodiments, the peptide X-Y-Z comprises a single modified amino acid or non-natural amino acid analogue.

[0109] Preferably, peptide moieties X and Y do not comprise any modified amino acids or non-natural amino acid analogues, and Z comprises 0, 1, 2, 3 or 4 modified amino acids or non-natural amino acid analogues. More preferably, peptide moieties X and Y do not comprise any modified amino acids or non-natural amino acid analogues, and Z comprises 0, 1, 2 or 3 modified amino acids or non-natural amino acid analogues. More preferably, peptide moieties X and Y do not comprise any modified amino acids or non- natural amino acid analogues, and Z comprises 0, 1 or 2 modified amino acids or non- natural amino acid analogues. Most preferably, peptide moieties X and Y do not comprise any modified amino acids or non-natural amino acid analogues, and Z comprises 0 or 1 modified amino acids or non-natural amino acid analogues.

[0110] Suitably, any modified amino acid or non-natural amino acid analogue in peptide moieties X, Y and / or Z is independently as defined in any one of paragraphs (39) to (43) above. More suitably, any modified amino acid or non-natural amino acid analogue in peptide moieties X, Y and / or Z is independently as defined in any one of paragraphs (41), (42) or (43) above. Most suitably, any modified amino acid or non-natural amino acid analogue in peptide moieties X, Y and / or Z is independently as defined in paragraph (43) above).

[0111] In a particular embodiment, the Z1group in Formula Z1 above is absent or is selected from F, Y or a modified amino acid or a non-natural amino acid analogue.

[0112] In certain embodiments, Y comprises no more than one modified amino acid or a non-natural amino acid analogue.

[0113] In certain embodiments, Z comprises no more than one modified amino acid or a non-natural amino acid analogue.

[0114] In certain embodiments, the peptide moieties X, Y and / or Z do not comprise any modified amino acid or non-natural amino acid analogues.

[0115] In certain embodiments, Z is a peptide moiety of the formula (Z1): Z1-S#-S#-W#-G#-Z6(Z1) (SEQ ID NO: 3) Z1is absent or is selected from F#or Y#; andZ6is absent or is G#.

[0116] In certain embodiments, Z has a formula selected from (Z1a), (Z1b), (Z1c), (Z1d) or (Z1e): S#-S#-W#-G#-G#(Z1a) (SEQ ID NO: 4) S#-S#-W#-G#(Z1b) (SEQ ID NO: 5) F#-S#-S#-W#-G#-G#(Z1c) (SEQ ID NO: 6) F#-S#-S#-W#-G#(Z1d) (SEQ ID NO: 7) Y#-S#-S#-W#-G#(Z1e) (SEQ ID NO: 8) wherein “ ” indicates that the residue is independently the listed unmodified amino acid, a modified amino acid or a non-natural amino acid analogue; and wherein Z comprises from 0 to 3 modified amino acids or a non-natural amino acid analogues.

[0117] In certain embodiments, Z has a formula selected from (Z2a), (Z2b), (Z2c), (Z2d) or (Z2e): S#-S#-W#-G-G (Z2a) (SEQ ID NO: 9) S#-S#-W#-G (Z2b) (SEQ ID NO: 10) F#-S#-W#-G-G (Z2c) (SEQ ID NO: 11) F#-S#-S#-W#-G (Z2d) (SEQ ID NO: 12) Y#-S#-S#-W#-G (Z2e) (SEQ ID NO: 13) wherein indicates that the residue is independently the listed unmodified amino acid, a modified amino acid or a non-natural amino acid analogue; and wherein Z comprises from 0 to 3 modified amino acids or a non-natural amino acid analogues.

[0118] In certain embodiments, Z has a formula selected from (Z3a), (Z3b), (Z3c), (Z3d) or (Z3e): S#-S-W-G-G (Z3a) (SEQ ID NO: 14) S#-S-W-G (Z3b) (SEQ ID NO: 15) F#-S-W-G-G (Z3c) (SEQ ID NO: 16) F#-S-S-W-G (Z3d) (SEQ ID NO: 17) Y#-S-S-W-G (Z3e) (SEQ ID NO: 18) wherein indicates that the residue is independently the listed unmodified amino acid, a modified amino acid or a non-natural amino acid analogue; and wherein Z comprises 0 or 1 modified amino acids or a non-natural amino acid analogues.

[0119] Suitably, in formulas (Z1a), (Z1b), (Z1c), (Z1d), (Z1e), (Z2a), (Z2b), (Z2c), (Z2d), (Z2e), (Z3a), (Z3b), (Z3c), (Z3d) or (Z3e) described herein any modified amino acids or a non-natural amino acid analogues are independently as defined in any one of paragraphs (39) to (43) above. More suitably, any modified amino acids or a non-natural amino acid analogues are independently as defined in any one of paragraphs (41), (42) or (43) above. More suitably, any modified amino acids or a non-natural amino acid analogues are independently as defined in paragraph (42) or (43) above.

[0120] Suitably, in formulas (Z1a), (Z1b), (Z1c), (Z1d) or (Z1e) described herein, any modified amino acids or a non-natural amino acid analogues are independently as defined in any one of paragraphs (39) to (43) above. More suitably, any modified amino acids or a non-natural amino acid analogues are independently as defined in any one of paragraphs (41), (42) or (43) above. More suitably, any modified amino acids or a non-natural amino acid analogues are independently as defined in paragraph (42) or (43) above.

[0121] Suitably, in formulas (Z2a), (Z2b), (Z2c), (Z2d) or (Z2e) described herein, any modified amino acids or a non-natural amino acid analogues are independently as defined in any one of paragraphs (39) to (43) above. More suitably, any modified amino acids or a non-natural amino acid analogues are independently as defined in any one of paragraphs (41), (42) or (43) above. More suitably, any modified amino acids or a non-natural amino acid analogues are independently as defined in paragraph (42) or (43) above.

[0122] Suitably, in formulas (Z3a), (Z3b), (Z3c), (Z3d) or (Z3e) described herein, any modified amino acids or a non-natural amino acid analogues are independently as defined in any one of paragraphs (39) to (43) above. More suitably, any modified amino acids or a non-natural amino acid analogues are independently as defined in any one of paragraphs (41), (42) or (43) above. More suitably, any modified amino acids or a non-natural amino acid analogues are independently as defined in paragraph (42) or (43) above.

[0123] Suitably, in some embodiments of the formulas described above, the “W#” residue is selected from a modified amino acid (i.e. a modified form of L-tryptophan) or a non-natural amino acid analogue, such as any of the modified amino acids or non-natural amino acid analogues described in paragraphs (39) to (43) above. More suitably, the W#group is [Nal].

[0124] Suitably, in formulas (Z3a), (Z3b), (Z3c), (Z3d) or (Z3e) described herein, the modified amino acid or a non-natural amino acid analogue is thienyl alanine (Thi).

[0125] In one embodiment, Z is a peptide moiety selected from: [n-me-S]S[Nal]GG (SEQ ID NO: 19); [n-me-S][s][Nal]GG (SEQ ID NO: 52); S-S-W-G-G (SEQ ID NO: 20);S-S-W-G (SEQ ID NO: 21); F-S-S-W-G-G (SEQ ID NO: 22); F-S-S-W-G (SEQ ID NO: 23); Y-S-S-W-G (SEQ ID NO: 24); [Thi]-S-S-W-G (SEQ ID NO: 25).

[0126] In one embodiment, Z is a peptide moiety selected from: S-S-W-G-G (SEQ ID NO: 20); S-S-W-G (SEQ ID NO: 21); F-S-S-W-G-G (SEQ ID NO: 22); F-S-S-W-G (SEQ ID NO: 23); Y-S-S-W-G (SEQ ID NO: 24).

[0127] In certain embodiments, Y-Z taken together form a peptide moiety with a formula selected from: LTFT[n-me-S]S[Nal]GG (SEQ ID NO: 44); LTFT[n-me-S][s][Nal]GG (SEQ ID NO: 53); LTFTSSWG (SEQ ID NO: 45); LTFFSSWGG (SEQ ID NO: 46); LTFFSSWG (SEQ ID NO: 47); LTFTFSSWG (SEQ ID NO: 48); LTFYSSWG (SEQ ID NO: 49); or LTF[Thi]SSWG (SEQ ID NO: 50).

[0128] In certain embodiments, Y-Z taken together form a peptide moiety with a formula selected from: LTFTSSWG (SEQ ID NO: 45); LTFFSSWGG (SEQ ID NO: 46); LTFFSSWG (SEQ ID NO: 47); LTFTFSSWG (SEQ ID NO: 48); or LTFYSSWG (SEQ ID NO: 49).

[0129] In one embodiment, the compound of the invention may be any of the bifunctional peptides or peptide analogues listed herein. Particular examples of bifunctionalpeptides and analogues include the compounds in the table below or salts or solvates thereof:

[0130] In certain embodiments of the invention the peptide is not [pyr]LTFT-SSWGG- NH2(SB-P-86, SEQ ID NO: 33).

[0131] In certain embodiments of the invention, if Y4is T, then Z6is absent

[0132] In certain embodiments of the invention, if Y4is T, and Z1is absent, then Z6is absent. Further Explanation of Compounds of the Invention

[0133] In some embodiments, the compounds of the invention may be in the form of a salt or solvate (e.g. a hydrate).

[0134] The compounds of the invention may be provided in combination with one or more additional active insecticides, such as those described herein. R1, L1and R2

[0135] The terminal groups present at the N- and C-termini of the peptide backbone are designated R1and R2respectively. Thus R1is bonded to the nitrogen atom of the N- terminal amino group of X (if present) or Y, and R2is bonded to the C-terminal carbonyl carbon atom of Z.

[0136] In addition to comprising at least one modified or unnatural amino acid residue, the compounds of the invention may include further functionalisation, suitably at the N or C terminus. Suitably, the compounds may be functionalised to increase cuticle permeability or to increase stability.

[0137] When R1= “H“ (or "Hy";), it typically indicates a free primary amino group at the N-terminus. The other hydrogen atom of the N-terminal amino group is typicallyinvariant, regardless of the nature of R1. Exceptionally, when the residue at the N-terminus is N-methylated, R1may still be indicated as H even though the N-terminal residue has a secondary amine group. Thus an N-methylated leucine residue at the N-terminus may be indicated as R1-[n-me-L]- where R1is H. However, it could also be shown as simply R1-L- where R1is methyl and the other hydrogen atom is not shown.

[0138] In some embodiments, R1may be a pyroglutamate group, [pyr]. Such a terminal residue may be formed by the conversion of an N-terminal glutamine (Gln or Q) or N-terminal glutamic acid (Glu or E) residue to form the pyroglutamate terminal group, [pyr]:An N-terminal glutamine (Q) or glutamic acid (E) residue may undergo such a conversion in biological systems via reaction with certain enzymes. The conversion may also be achieved synthetically. Since this conversion may occur under certain biological conditions, 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.

[0139] Thus, in certain embodiments, R1is a pyroglutamate terminal group. Thus, in the peptides described herein, the notation [pyr] refers to the following structure:.

[0140] In preferred embodiments, if R1is a pyroglutamate, then X is absent.

[0141] In preferred embodiments, if X is Q#or E#, then R1is hydrogen.

[0142] In certain embodiments, R2is NH2, NR2aH or NR2aR2b, wherein each of R2aand R2bif present is independently selected from C1-2-alkyl. Preferably R2is NH2or NMe2. More preferably R2is NH2. Modified amino acid or non-natural amino acid analogue

[0143] In certain embodiments, at least one of the residues in peptides Y and Z is a modified or non-natural amino acid analogue. The modified or non-natural amino acid analogue may be any analogue known to a skilled person. Examples of modified or non- natural amino acid analogues include:i. N-methylated amino acid; ii. a peptoid analogue; iii. a sugar modified analogue; iv. a biotin modified analogue v. beta amino acids, vi. D-configuration amino acid, vii. non- proteinogenic amino acids, such as hydroxyproline (Hyp: L- hydroxyproline or (2S,4R)-4-Hydroxyproline), Octahydroindole-2-carboxylic acid (Oic), sarcosine (Sar), norleucine (Nle), α-aminoisobutyric acid (Aib), thienyl alanine (Thi), thiazolidine-4-carboxylic acid (Thz), phenylglycine (Phg), naphthylalanine (Nal) or gamma aminobutyric acid (gaba), etc. viii α-alkylated amino acids; or the side chains of two amino acid residues may be joined together to form a cyclic structure (e.g. intramolecular amide formation via condensation reaction between the side chains of arginine or lysine, with the side chain of aspartic acid or glutamic acid.

[0144] The compounds of the invention may comprise one or more modified amino acid or non-natural amino acid analogues in the Y peptide, the Z peptide or both the Y and Z peptides.

[0145] In certain embodiments, at least one of the residues in the Y moiety is a modified or non-natural amino acid analogue.

[0146] The compounds of the invention may comprise multiple modified amino acid or non-natural amino acid analogues in the peptide sequence Y-Z.

[0147] In other embodiments, the peptide Y-Z comprises only unmodified amino acids, i.e. each residue is the listed proteinogenic amino acid residue. Activity

[0148] Suitably, the compounds of the invention have activity against insects. Suitably the activity is against hemipteran, dipteran, lepidopteran, blattodea and / or coleopteran insects. More suitably, the activity is against lepidopteran insects.

[0149] Suitably, the compounds have activity against hemipteran insects, dipteran insects and / or lepidopteran insects. The compounds of the invention may therefore find particular use against hemipteran insects, dipteran insects and / or lepidopteran insects such as those described herein.

[0150] More suitably, the compounds have activity against lepidopteran insects. The compounds of the invention may therefore find particular use against lepidopteran insects such as those described herein.

[0151] The compounds typically increase insect mortality, for example when contacted topically to a suitable insect, or ingested by a suitable insect. Thus, thecompounds described (and compositions containing them) may be regarded as insecticides, and may be referred to as "insect control agents".

[0152] Without wishing to be bound by theory, any or all of the effects described may be mediated by agonist activity at an AKH and / or a kinin receptor of the target insects. Suitably the compounds of the invention have agonist activity when bound to an AKH receptor and / or a kinin of a target insect.

[0153] In general, the peptides of the invention demonstrate a LogEC50of -5.0 (equivalent to 10 µM) or less in the kinin receptor activation assay described herein, with preferred compounds of the invention demonstrating an LogEC50 of -6.0 (equivalent to 1 µM) or less and the most preferred compounds of the invention demonstrating an LogEC50 of - 6.5 (equivalent to 0.3 µM) or less.

[0154] In general, the peptides of the invention demonstrate a LogEC50 of -5.0 (equivalent to 10 µM) or less in the AKH receptor activation assay described herein, with preferred compounds of the invention demonstrating an LogEC50 of -5.5 (equivalent to 3 µM) or less and the most preferred compounds of the invention demonstrating an LogEC50 of - 6.0 (equivalent to 1 µM) or less. Insect control agent

[0155] The term “insect control agent” refers to agents used to increase insect mortality (i.e. as insecticides). Any compound or composition thereof of the invention maybe considered as an insect control agent, and may be used as an insect control agent. Suitably therefore the invention provides the use of a compound or composition of the invention as an insect control agent, for example against diptera insects, hemiptera insects, coleoptera insects, blattodea insects, and / or lepidoptera insects. Thus an insect control agent may be administered to increase mortality of a given insect or insect population.

[0156] An increase in mortality used herein is intended to refer to an increase in the percentage of dead insects, as compared to the percentage of dead insects of an otherwise identical insect population which have not been exposed to the insect control agent of the invention.

[0157] Suitably, insect mortality may be calculated as number of dead insects / total number of insects per treated area. Suitably the treated area may be a well of a plate, or may be one or more leaves, or an entire plant. Suitably insect mortality may be measured by performing a leaf dip assay as described herein in the examples.

[0158] An insect control agent may be used to reduce the size of an insect population, or inhibit growth of an insect population or inhibit feeding of an insect population (e.g. as compared to an otherwise identical insect population not exposed to the agent).

[0159] An insect control composition is a composition comprising an insect control agent i.e. a compound of the invention as described.Plant protection agent

[0160] The term “plant protection agent” refers to agents used to protect a plant or plant part against insects, e.g. against infestation or colonisation, or being used as a food source by such insects (e.g. by the draining of sap). Any compound or composition thereof of the invention maybe considered as a plant protection agent, and may be used as a plant protection agent. Suitably therefore the invention provides the use of a compound or composition of the invention as a plant protection agent, for example to protect a plant against diptera insects, hemiptera insects, coleoptera insects, blattodea insects, and / or lepidoptera insects.

[0161] Infestation or colonisation may be by larvae (or nymphs), by adult insects, or may be by being used as a host or repository for eggs. The terms “infestation” and “colonisation” should not be construed as requiring the presence of the insects to be deleterious to the plant, however.

[0162] A plant protection agent may be applied inter alia for reducing insect load on a plant or plant part, for inhibiting or reducing infestation of a plant by insects, for inhibiting (e.g. reducing the rate of) an increase in insect load on a plant or plant part, or for maintaining a plant in an insect-free state, as compared to an otherwise identical plant having an insect population not exposed to the agent. Thus, the plant protection agent may be applied to a plant or plant part which already carries hemipteran, dipteran coleoptera insects, blattodea insects, and / or lepidopteran insects, or to a plant or plant part which is free or substantially free of hemipteran, dipteran and / or lepidopteran insects.

[0163] A plant protection composition is a composition comprising a plant protection agent i.e. a compound of the invention as described. Plants

[0164] By ‘plant or plant part’, or ‘plant or part thereof’ referred to herein it is meant any part of a plant including but not limited to; the leaf, stem, root, flower, bud, bulb, and seed.

[0165] Suitable plants or parts thereof which may be protected by the compounds or compositions thereof of the invention, or by the agents of the present invention include crops and plants of agricultural, horticultural, or economic significance. Suitable plants may include any of the following or parts thereof: Musa textilis, Medicago sativa, Prunus dulcis, Pimpinella anisum, Malus sylvestris, Prunus armeniaca, Areca catechu, Arracacia xanthorhiza, Maranta arundinacea, Cynara scolymus, Helianthus tuberosus, Asparagus officinalis, Persea americona, Pennisetum americanum, Vigna subterranean, Musa paradisiaca, Hordeum vulgare, Phaseolus vulgaris, Phaseolus vigna spp., Beta vulgaris, Citrus bergamia, Rubus spp., Piper nigrum, Acacia mearnsii, Vaccinium spp., Bertholletia excelsa, Artocarpus altilis, Vicia faba, Brassica oleraceabotrytis, Sorghum bicolor, Brassica oleracea gemmifera, Fagopyrum esculentum, Brassica oleracea capitate, Brassica rapa, Brassica spp., Theobroma cacao, Cucumis melo, Carum carvi, Elettaria cardamomum, Cynara cardunculus, Ceratonia siliqua, Daucus carota, Anacardium occidentale, Manihot esculenta, Ricinus communis, Brassica oleracea botrytis, Apium graveolens, Sechium edule, Prunus spp., Castanea sativa, Cicer arietinum, Cichorium intybus, Cichorium intybus, Capsicum spp., Cinnamomum verum, Cymbopogon nardus, Citrus medica, Citrus veticulata, Trifolium spp., Syzygium aromaticum, Cocos nucifera, Colocasia spp.; Xanthosoma spp., Coffee spp., Cola spp., Brassica napus, Zea mays, Valerianella locusta, Gossypium spp., Vigna unguiculate, Vaccinium spp., Lepidium sativum, Cucumis sativus, Ribes spp., Annona reticulata, Colocasia esculenta, Phoenix dactylifera, Moringa oleifera, Phaseolus spp., Allium sativum, Allium cepa, Pisum sativum, Triticum durum, Xanthosoma spp.; Colocasia spp., Solanum melongena, Cichorium endivia, Lygeum spartum, Foeniculum vulgare, Trigonella foenumgraecum, Ficus carica, Corylus avellane, Furcraea macrophylla, Linum usitatissimum, Phormium tenax, Pelargonium spp.; Geranium spp., Zingiber officinalis, Langenaria spp; Cucurbita spp., Cicer arietinum, Citrus paradise, Vitis vinifera, Lygeum spartum, Dactylis glomerata, Arachis hypogaea, Psidium guajava, Corylus avellane, Cannabis sativa, Crotalaria juncea, Agave fourcroydes, Lawsonia inermis, Humulus lupulus, Armoracia Rusticana, Indigofera tinctorial, Jasminum spp., Corchorus spp., Brassica oleracea acephala, Ceiba pentandra, Hibiscus cannabinus, Brassica oleracea gongylodes, Lavandula spp., Allium ampeloprasum, Citrus limon, Cymbopogon citratus, Lens culinaris, Lespendeza spp., Lactuca sativa, Glycyrrhiza glabra, Citrus aurantifolia, Citrus limetta, Linum usitatissimum, Litchi chinensis, Eriobotrya japonica, Lupinus spp., Macadamia spp., Myristica fragrans, Agave atrovirens, Citrus reticulata, Mangifera indica, Manihot esculenta, Secale cereal, Mespilus germanica, Cucumis melo, Penicum miliaceum, Eleusine coracana, Setaria italica, Echinochloa crusgalli, Eleusine coracana; Mentha spp., Morus spp., Morus alba, Agaricus spp.; Pleurotus spp. Volvariella, Brassica nigra; Sinapis alba, Prunus persica, Phormium tenax, Guizotia abyssinica, Myristica fragrans, Avena spp., Elaeis guineensis, Abelmoschus esculentus, Olea europea, Papaver somniferum, Citrus sinensis, Citrus aurantium, Dactylis glomerate, Metroxylon spp., Borassus flabellifer, Carica papaya, Pastinaca sativa, Pyrus communis, Pisum sativum, Carya illinoensis, Capsicum annuum, Diospyros kaki; Diospyros virginiana, Cajanus cajan, Ananas comosus, Pistacia spp., Prunus domestica, Punica granatum, Citrus grandis, Solamum tuberosum, Ipomoea batatas, Cucurbita spp., Chrysanthemum cineraraiefolium, Aspidosperma spp., Cydonia oblonga, Cinchona spp., Chenopodium quinoa, Raphanus sativus (including Cochlearia armoracia), Boehmeria nivea, Agrostis spp., Boehmeria nivea, Rheum spp., Oryza sativa; Oryza glaberrima, Rose spp., Hevea brasiliensis, Secale cereal, Lolium spp., Carthamus tinctorius, Metroxylon spp., Onobrychis viciifolia, Valerianellalocusta, Tragopogon porrifolius, Achras sapota, Citrus reticulata, Brassica ileracea capitate, Scorzonera hispanica, Sesamum indicum, Butyrospermum paradoxum, Agave sislana, Citrus aurantifolia, Glycine max, Triticum spelta, Spinacia oleracea, Secale cereal, Cucurbita spp., Fragaria spp., Sorghum bicolor Sudanense, Saccharum officinarum, Helianthus annuus, Crotalaria juncea, Citrus limetta, Iopmoea batatas, Citrus reticulata, Xanthosoma sagittifolium, Manihot esculenta, Colocasia esculenta, Camellia sinensis, Eragrostis abyssinica, Phleum pratense, Nicotiana tabacum, Lycopersicum esculentum, Lotus spp., Aleurites spp., Brassica rapa, Urena lobate, Vanilla planifolia, Vicia sativa, Juglans spp., Citrullus lanatus, Acacia mearnsii, Triticum spp., Hordeum spp., Dioscorea spp., and Ilex paraguariensis.

[0166] Suitably, the plant or part thereof which may be protected by the compounds, compositions, or agents of the present invention is selected from a plant or part thereof which suffers from hemipteran, dipteran, lepidopteran, blattodea and / or coleopteran insect infestations, or which attracts hemipteran, dipteran, lepidopteran, blattodea and / or coleopteran insects. Suitably, the plant or part thereof which suffers from hemipteran, dipteran, lepidopteran, blattodea and / or coleopteran insect infestations, or hemipteran, dipteran, lepidopteran, blattodea and / or coleopteran insects is any of those listed above.

[0167] Suitably, the plant or part thereof which suffers from hemipteran insect infestations, or which attracts hemipteran insects, is any of those listed above.

[0168] Suitably, the plant or part thereof which suffers from dipteran insect infestations, or which attracts dipteran insects, is any of those listed above.

[0169] Suitably, the plant or part thereof which suffers from lepidopteran insect infestations, or which attracts lepidopteran insects, is any of those listed above.

[0170] Suitably, the plant or part thereof which suffers from coleopteran insect infestations, or which attracts coleopteran insects, is any of those listed above.

[0171] In one embodiment, the plant or part thereof is selected from a plant or part thereof which suffers from or attracts hemipteran insect infestations, for example: cereal crops such as wheat (Triticum spp.), oats (Avena spp), rye (Secale spp.), barley (Hordeum spp.), rice (Oryza spp.) and corn (Zea spp.); fruit and vegetable crops including apples (Malus spp); pears (Pyrus spp); strawberry (Fragaria spp.), blueberry (Vaccinum spp.), blackberry (Rubus spp.), raspberry (Rubus spp.), citrus (Citrus spp.), olive (Olea spp.), durian (Durio spp.), longan (Dimocarpus spp.), litchi (L. chinensis), persimmon (Diospyros 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 (Brassica spp.) including oil seed rape, alliums (Allium spp.), tomato (Solanum spp.), pepper (Capsicum spp.), asparagus (A. officinalis), melon, squash, pumpkins (Cucumis spp.), and tubers (potato) (Solanum spp.), or a part thereof.

[0172] In one embodiment, the plant or part thereof is selected from a plant or part thereof which suffers from or attracts aphid insect infestations, suitably M. persicae insect infestations, including Solanaceae, Cruciferae, and Leguminosae for example: cereal crops such as wheat (Triticum spp including winter wheat Triticum aestivum L); fruit and vegetable crops including peach (Prunus spp.), strawberry (Fragaria spp.), blueberry (Vaccinum spp.), blackberry (Rubus spp.), raspberry (Rubus spp.), brassicas (Brassica spp.) such as oil seed rape, lettuce (Lactuca spp.), tomato (Solanum spp.), pepper (Capsicum spp.), beans and peas (including but not limited to Vigna, Pisum spp), melon, squash, pumpkins (Cucumis spp.), citrus (Citrus spp.), and tubers (potato) (Solanum spp.), or a part thereof. In one embodiment, the plant is a vegetable crop, suitably a brassica spp.

[0173] In one embodiment, the plant or part thereof is selected from a plant or part thereof which suffers from or attracts dipteran insect infestations, for example: cereals (Triticum spp.); oats (Avena spp);, rye (Secale spp.); barley (Hordeum spp,) rice (Oryza spp.) and corn (Zea spp.); beans and peas (including but not limited to Phaseolus, Vigna, Pisum, Lens, Glycine, Cicer, Cajanus, Arachis spp); fruit crops including apples (Malus spp), pears (Pyrus spp), strawberry (Fragaria spp.), blueberry (Vaccinum spp.), blackberry (Rubus spp.), raspberry (Rubus spp.), cherry, plum, apricot, peach, nectarine (Prunus spp.), blackcurrant, redcurrant, whitecurrant, gooseberry (Ribes spp.), kiwi fruit (Actinidia spp), papaya (Carica spp.), avocado (Persea spp.), mango (Mangifera indica L), longan (Dimocarpus spp.), litchi (L. chinensis), grapes (Vitis spp.), fig (Ficus spp.), passionfruit (Passiflora spp.), Asian pears (Pyrus spp), citrus (Citrus spp.), and olive (Olea spp.); vegetable crops including alliums (Allium spp.), aubergine, tomato (Solanum spp.) and peppers (Capsicum spp.), lettuce (Lactuca spp.), brassicas (Brassica spp.) and courgette, melon, squash, pumpkins (Cucumis spp.); Apiaceae root crops including carrot (Daucus spp.), parsnip (Pastinaca spp.), or a part thereof.

[0174] In one embodiment, the plant or part thereof is selected from a plant of part thereof which suffers from or attracts lepidoptera insect infestations, for example: cereal crops such as wheat (Triticum spp.), oats (Avena spp), rye (Secale spp.), barley (Hordeum spp.), rice (Oryza spp.) and corn (Zea spp.); fruit and vegetable crops including apples (Malus spp); pears (Pyrus spp); tree nuts (including for example almonds (P. amygdalus), pistachio (Pistacia vera), walnuts (Juglandaceae), hazlenuts (Corylus)); avocado, including Persea Americana (Lauraceaea), blueberry (Vaccinum spp.), citrus (Citrus spp.), olive (Olea spp.), durian (Durio spp.), longan (Dimocarpus spp.), litchi (L. chinensis), persimmon (Diospyros 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 (Brassica spp.) including oil seed rape, alliums (Allium spp.), tomato (Solanum spp.), pepper (Capsicum spp.), asparagus (A.officinalis), melon, squash, pumpkins (Cucumis spp.), and tubers (potato) (Solanum spp.), or a part thereof. Insects

[0175] The compounds, compositions, and agents of the invention suitably have activity against insects as described above.

[0176] The compounds, compositions, and agents of the invention may be effective against any insects. Such as Arthropoda, in particular from the class of the arachnids, 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 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., 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.

[0177] Still other examples are from the order of the Anoplura (Phthiraptera), for example, Damalinia spp., Haematopinus spp., Linognathus spp., Pediculus spp., Ptirus pubis, Trichodectes spp.

[0178] Still other examples are from the order of the Chilopoda, for example, Geophilus spp., Scutigera spp.

[0179] Still other examples are from the order of the Coleoptera, for example, Acalymma vittatum, Acanthoscelides obtectus, Adoretus spp., Agelastica alni, Agriotes spp., Alphitobius diaperinus, Amphimallon solstitialis, Anobium punctatum, Anoplophora spp., Anthonomus spp., Anthrenus 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., 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., Lachnosterna consanguinea, Lema spp., Leptinotarsa decemlineata, Leucoptera spp., Lissorhoptrus oryzophilus, Lixus spp., Luperodes spp., Lyctus spp., Megascelis spp., Melanotus spp., Meligethes aeneus, Melolontha spp., Migdolus spp., Monochamus spp., Naupactus xanthographus, Niptus hololeucus, Oryctesrhinoceros, Oryzaephilus surinamensis, Oryzaphagus oryzae, Otiorrhynchus spp., Oxycetonia jucunda, Phaedon cochleariae, Phyllophaga spp., Phyllotreta spp., Popillia japonica, Premnotrypes spp., Prostephanus truncatus, Psylliodes spp., Ptinus spp., Rhizobius ventralis, Rhizopertha dominica, Sitophilus spp., Sphenophorus spp., Stegobium paniceum, Sternechus spp., Symphyletes spp., Tanymecus spp., Tenebrio molitor, Tribolium spp., Trogoderma spp., Tychius spp., Xylotrechus spp., Zabrus spp. Suitably compounds, compositions, and agents of the invention have activity against Coleoptera species selected from, for example: Bruchid beetle (Bruchus rufimanus), cabbage seed weevil (Ceutorhynchus obstrictus), cabbage stem flea beetle (Psylliodes chrysocephalus), cabbage stem weevil (Ceutorhynchus pallidactylus), Chafer grubs (Melolontha melolontha), Colorado potato beetle (Leptinotarsa decemlineata), pea and bean weevils (Sitona lineatus), pollen beetle (Meligethes spp.), pygmy beetle (Atomaria linearis), rape winter stem weevil (Ceutorhynchus picitarsis), and wireworms (Agriotes spp.).

[0180] Still other examples are from the order of the Collembola, for example, Onychiurus armatus.

[0181] Still other examples are from the order Blattodea, for example B. germanica, Blatta orientalis, Periplaneta America, Periplaneta spp., Supella longipalpa and Supella longipalpa; also those of the family termitidae.

[0182] Still other examples are from the order of the Diplopoda, for example, Blaniulus guttulatus.

[0183] Still other examples are from the order of the 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., 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., Fannia spp., Gasterophilus spp., Glossina 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., Tannia spp., Tetanops spp., Tipula spp. Still other examples are from the order of the Heteroptera, for example, Anasa tristis, Antestiopsis spp., Boisea spp., Blissus spp., Calocoris spp., Campylomma livida, Cavelerius spp., Cimex spp., Collaria spp., Creontiades dilutus, Dasynus piperis, Dichelops 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., Sahlbergella singularis, Scaptocoris castanea, Scotinophora spp., Stephanitis nashi, Tibraca spp., Triatoma spp. Still other examples are from the order of the Homoptera, for example, Acyrthosipon spp., Acrogonia spp., Aeneolamia spp., Agonoscena spp., Aleurodes spp., Aleurolobus barodensis, Aleurothrixus spp., Amrasca spp., Anuraphis cardui, Aonidiella spp., Aphanostigma pin, Aphis spp., Arboridia apicalis, Aspidiella spp., Aspidiotus spp., Atanus spp., Aulacorthum solani, Bemisia spp., Brachycaudus helichrysii, Brachycolus spp., Brevicoryne brassicae, Calligypona marginata, Carneocephala fulgida, Ceratovacuna lanigera, Cercopidae, Ceroplastes spp., Chaetosiphon fragaefolii, Chionaspis 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., 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., 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., Peregrinus maidis, Phenacoccus spp., Phloeomyzus passerinii, Phorodon humuli, Phylloxera spp., Pinnaspis aspidistrae, Planococcus spp., Protopulvinaria pyriformis, Pseudaulacaspis pentagona, Pseudococcus spp., Psylla spp., Pteromalus spp., Pyrilla spp., Quadraspidiotus spp., Quesada gigas, Rastrococcus spp., Rhopalosiphum spp., Saissetia spp., Scaphoides titanus, Schizaphis graminum, Selenaspidus articulatus, Sogata spp., Sogatella furcifera, Sogatodes spp., Stictocephala festina, Tenalaphara malayensis, Tinocallis caryaefoliae, Tomaspis spp., Toxoptera spp., Trialeurodes spp., Trioza spp., Typhlocyba spp., Unaspis spp., Viteus vitifolii, Zygina spp.

[0184] Still other examples are from the order of the Hymenoptera, for example, Acromyrmex spp., Athalia spp., Atta spp., Diprion spp., Hoplocampa spp., Lasius spp., Monomorium pharaonis, Solenopsis invicta, Tapinoma spp., Vespa spp.

[0185] Still other examples are from the order of the Isopoda, for example, Armadillidium vulgare, Oniscus asellus, Porcellio scaber.

[0186] Still other examples are from the order of the Isoptera, for example, Coptotermes spp., Cornitermes cumulans, Cryptotermes spp., Incisitermes spp., Microtermes obesi, Odontotermes spp., Reticulitermes spp.

[0187] Still other examples are from the order of the Lepidoptera, for example, Acronicta major, Adoxophyes spp., Aedia leucomelas, Agrotis spp., Alabama spp., Amyeloistransitella, Anarsia spp., Anticarsia spp., Argyroploce spp., Barathra brassicae, Borbo cinnara, Bucculatrix thurberiella, Bupalus 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., 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 mellonella, Gracillaria spp., Grapholitha spp., Hedylepta spp., Helicoverpa spp., Heliothis spp., Hofmannophila pseudospretella, Homoeosoma spp., Homona spp., Hyponomeuta padella, Kakivoria flavofasciata, Laphygma spp., Laspeyresia 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., Phthorimaea spp., Phyllocnistis citrella, Phyllonorycter spp., Pieris spp., Platynota stultana, Plodia interpunctella, Plusia spp., Plutella xylostella, Prays spp., Prodenia spp., Protoparce spp., Pseudaletia spp., Pseudoplusia includens, Pyrausta nubilalis, Rachiplusia nu, Schoenobius spp., Scirpophaga spp., Scotia segetum, Sesamia spp., Sparganothis spp., Spodoptera frugiperda, Spodoptera spp., Stathmopoda spp., Stomopteryx subsecivella, Synanthedon spp., Tecia solanivora, Thermesia gemmatalis, Tinea pellionella, Tineola bisselliella, Tortrix spp., Trichophaga tapetzella, Trichoplusia spp., Tuta absoluta, Virachola spp.

[0188] Still other examples are from the order of the Orthoptera, for example, Acheta domesticus, Dichroplus spp., Gryllotalpa spp., Leucophaea maderae, Locusta spp., Melanoplus spp., ., Pulex irritans, Schistocerca gregaria, .

[0189] Still other examples are from the order of the Siphonaptera, for example, Ceratophyllus spp., Ctenocephalides spp., Tunga penetrans, Xenopsylla cheopis.

[0190] Still other examples are from the order of the Symphyla, for example, Scutigerella spp.

[0191] Still other examples are from the order of the Thysanoptera, for example, Anaphothrips obscurus, Baliothrips biformis, Drepanothris reuteri, Enneothrips flavens, Frankliniella spp., Heliothrips spp., Hercinothrips femoralis, Rhipiphorothrips cruentatus, Scirtothrips spp., Taeniothrips cardamoni, Thrips spp. Still other examples are from the order of the Zygentoma (=Thysanura), for example, Lepisma saccharina, Thermobia domestica. for example Lepisma saccharina, Thermobia domestica.

[0192] In one preferred embodiment, the compounds, compositions, and agents ofthe invention suitably have activity against insects of the order hemiptera, diptera and / or lepidoptera. In one preferred embodiment, the compounds, compositions, and agents of the invention suitably have activity against insects of the order Hemiptera. In one preferred embodiment, the compounds, compositions, and agents of the invention suitably have activity against aphids. In one embodiment, the compounds, compositions, and agents of the invention suitably have activity against the aphid species Myzus persicae. Hemipteran insects

[0193] The compounds, compositions and agents of the invention suitably have activity against insects of the order Hemiptera, which comprises groups including aphids, planthoppers, leafhoppers, stink bugs, shield bugs and cicadas. Suitably, the compounds, compositions and agents of the invention suitably have activity against aphids.

[0194] Hemipterans are defined by distinctive mouthparts in the form of a “beak”, comprising modified mandibles and maxillae which form a “stylet”, sheathed within a modified labium.

[0195] Many insects within these groups have endogenous neuropeptides with sequence homology to the peptides described herein, suggesting that the compounds of the present invention may have activity against those insects.

[0196] The insects may belong to the sub-order Sternorrhyncha, e.g. to the super- family of Aphidoidea (aphid superfamily), Aleyrodoidea (whiteflies), Coccoidea (scale insects), Phylloxeroidea (including Phylloxeridae or “phylloxerans”, and Adelgidae or woolly conifer aphids) or Psylloidea (jumping plant lice etc.).

[0197] Thus, the insects may be aphids, i.e. members of the aphid superfamily (Aphidoidea). Aphids (Hemiptera: Aphididae) are one of the most significant groups of agricultural pests and are vectors in the transmission of approximately 50% of all insect transmitted plant viruses. Within that superfamily, the aphids may be part of the family Aphididae, which contains sub-families Aiceoninae, Anoeciinae, Aphidinae, Baltichaitophorinae, Calaphidinae, Chaitophorinae, Drepanosiphinae, Eriosomatinae, Greenideinae, Hormaphidinae, Israelaphidinae, Lachninae, Lizeriinae, Macropodaphidinae, Mindarinae, Neophyllaphidinae, Phloeomyzinae, Phyllaphidinae, Pterastheniinae, Saltusaphidinae, Spicaphidinae, Taiwanaphidinae, Tamaliinae and Thelaxinae.

[0198] The aphids may, for example, be of the genus Acyrthosiphon (e.g. Acyrthosiphon pisum), Aphis (e.g. Aphis gossypii, Aphis glycines), Diuraphis (e.g. Diuraphis noxia) Macrosiphum (e.g. Macrosiphum rosae, Macrosiphum euphorbiae), Myzus (e.g. Myzus persicae), Rhopalosiphum (e.g. Rhopalosiphum padi), or Sitobion (e.g. Sitobion avenae).

[0199] Myzus persicae (peach potato aphid) is the most economically important aphid crop pest worldwide, with a global distribution and host range encompassing morethan 400 species in 40 different plant families. For example, it is a major pest of agricultural crops including fruit and potatoes, and act as a vector for viruses.

[0200] Macrosiphum rosae, (rose aphid) is an important horticultural pest, especially of cultivated species of Rosa, and is a vector in the transmission of 12 plant viruses including the strawberry mild yellow edge virus.

[0201] Aphis gossypii (cotton or melon aphid) is a pest of Curcibitae and cotton.

[0202] Other than aphids, the insects may, for example, be of the Adelgidae family, e.g. of the genus Adelges (e.g. Adelges tsugae).

[0203] The insects may be of the Aleyrodidae family, e.g. of the genus Bemisia (e.g. Bemisia tabaci) or Trialeurodes (e.g. Trialeurodes vaporariorum).

[0204] The insects may be of the Psylloidea family, e.g. of the genus Pachypsylla (e.g. Pachypsylla venusta).

[0205] As examples of hemipteran insects outside the sub-order Sternorryncha, the insects may be of the Cimicidae family, e.g. of the genus Cimex (bed bugs), e.g. Cimex lectularius.

[0206] The insects may be of the Cicadellidae family, e.g. of the genus Cuerna (e.g. Cuerna arida), Graminella (e.g. Graminella nigrifrons) or Homalodisca (e.g. Homalodisca vitripennis). Also included in the Cicadellidae family are Amrasca biguttula.

[0207] The insects may be part of the Delphacidae family, e.g. of the genus Nilaparvata (e.g. Nilaparvata lugens) or Sogatella (e.g. Sogatella furcifera). For example, Nilaparvata lugens (brown planthopper) is a pest of rice crops, especially in Asia.

[0208] The insects may be of the Liviidae family, e.g. of the genus Diaphorina (e.g. Diaphorina citri).

[0209] The insects may be part of the Miridae family, e.g. of the genus Pseudatomoscelis (e.g. Pseudatomoscelis seriatus), Lygus (e.g. Lygus hesperus) or Tupiocoris (e.g. Tupiocoris notatus). For example, Pseudatomoscelis seriatus (cotton fleahopper) is a pest of cotton.

[0210] The insects may be of the Pentatomidae family, e.g. of the genus 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 viridula), Plautia (e.g. Plautia stali), or Podisus (e.g. Podisus maculiventris). For example, Acrosternum hilare (green stink bug) is a significant 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 USA. Nezara viridula is a pest of grain and soybean crops, especially in Brazil.

[0211] The insects may be of the Pyrrhocoridae family, e.g. of the genus Pyrrhocoris (e.g. Pyrrhocoris apterus).

[0212] The insects may be of the Reduviidae family, e.g. of the genus Rhodnius (e.g. Rhodnius prolixus), or Triatoma (e.g. Triatoma infestans). Rhodnius prolixus is a vector of human disease (Chagas disease).

[0213] The insects may be of the Triozidae family, e.g. of the genus Acanthocasuarina (e.g. Acanthocasuarina muellerianae).

[0214] 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, and R. prolixus.

[0215] In one embodiment, the insect is of the species Nilaparvata lugens. In one embodiment, the compounds, compositions and agents of the invention may have activity against Nilaparvata lugens.

[0216] In one embodiment, the insect is of the species M. persicae. In one embodiment, the compounds, compositions and agents of the invention may have activity against M. persicae. Dipteran insects

[0217] The compounds, compositions and agents of the invention may have activity against insects of the order Diptera.

[0218] In particular, they may have activity against insects of the family Drosophilidae, such as fruit flies, including those of genus Drosophila, such as 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.); Tephritis (Tephritis spp.).

[0219] The families Drosophilidae and Tephritidae together are commonly referred to as fruit flies.

[0220] The compounds, compositions, and agents may also have activity against other important dipteran pests, such as flies of the family Chloropidae (chloropid flies) and those of the genera: Phytomyza (e.g. Phytomyza angelicastri); Melani (e.g. Melani agromyza); Antherigona (e.g. Antherigona spp); Delia (e.g. Delia radicum); Contarinia (e.g. Contarinia sorghicola);

[0221] For more detail on these, and other examples, see Developing the Arsenal Against Pest and Vector Dipterans: Inputs of Transgenic and Paratransgenic Biotechnologies, Ogaugwu and Durvasula, IntechOpen, 2017: DOI:10.5772 / 66440 Blattodea Insects

[0222] The compounds, compositions and agents of the invention may have activity against insects of the order Blattodea, for example B. germanica, Blatta orientalis, Periplaneta America and Supella longipalpa.

[0223] In particular, they may have activity against insects of the genera Blattella. Suitably, the Suitably the compounds, compositions and agents of the invention may have activity against the species Blattella germanica.

[0224] In one embodiment, the compounds, compositions and agents of the invention may have activity against Blattella germanica. Lepidopteran Insects

[0225] The compounds, compositions and agents of the invention may have activity against insects of the order Lepidoptera.

[0226] 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., Spodoptera frugiperda, and Cydia pomonella (Codling Moth), Larvae of Heliothis spp., including peltigera and virescens Spodoptera littoralis (which represent a large variety of Heliothinae and Spodoptera moth species and are world-wide agricultural pests), and Plutella xylostella (diamondback moth, most important world-wide pest of Brassicas).

[0227] In one embodiment, the compounds, compositions and agents of the invention may have activity against Plutella xylostella.

[0228] In one embodiment, the compounds, compositions and agents of the invention may have activity against Spodoptera frugiperda. Coleopteran Insects

[0229] The compounds, compositions and agents of the invention may have activity against insects of the order Coleoptera.

[0230] 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 agents of the invention may have activity against the species: Bruchid beetle (Bruchus rufimanus), cabbage seed weevil (Ceutorhynchus obstrictus), cabbage stem flea beetle (Psylliodes chrysocephalus), cabbage stem weevil (Ceutorhynchus pallidactylus), Chafer grubs (Melolontha melolontha), Colorado potato beetle (Leptinotarsa decemlineata), pea and bean weevils (Sitona lineatus), pollen beetle (Meligethes spp.), pygmy beetle (Atomaria linearis), rape winter stem weevil (Ceutorhynchus picitarsis), and wireworms (Agriotes spp.) Household Pests

[0231] The compounds, compositions, and agents of the invention may also have activity against domestic pests, such as cockroaches and termites. Of more than 3000 species, these may include the German cockroach (Blattella germanica), the Oriental cockroach (Blatta orientalis), the American cockroach (Periplaneta americana) and the brown banded cockroach (Supella longipalpa). Cockroaches are common domestic pests worldwide, and may carry various diseases. Control of these and other domestic pests (e.g. ants) is envisaged by treating surfaces where the insects run, but particularly with food baits containing compounds, compositions and agents of the invention, and with direct spray application of compounds, compositions and agents of the invention.

[0232] Therefore further aspects of the invention may include a bait comprising a compound or composition of the invention, suitably which may be a bait for domestic pests. Further aspects of the invention may include a method of controlling domestic pests, reducing domestic pest populations, inhibiting domestic pest populations, increasing domestic pest mortality, the method comprising treating a surface (e.g. wood) which is contacted by the domestic pest with a compound or composition of the invention, or contacting the domestic pest with a compound or composition of the invention. Further details of such methods are described hereinbelow. Optionally treating or contacting may comprise a suitable means of application as described elsewhere herein, such as by spraying. Suitably therefore a sprayable formulation comprising a compound or composition of the invention is also envisaged. Suitable formulations are described elsewhere herein. Methods and Uses of the Invention Methods of Increasing Insect Mortality

[0233] The invention provides a method of increasing insect mortality, comprising contacting an insect or insect population with a compound, composition or combinations as described herein. The insect or insect population may be hemipteran, dipteran, lepidopteran, blattodea and / or coleopteran insects. Preferably, the insect population is a lepidopteran insect population.

[0234] In one embodiment, there is provided a method of increasing lepidoptera insect mortality, comprising contacting a lepidopteran insect or lepidopteran insect population with a compound or composition or combinations as defined herein.

[0235] In one particular embodiment, there is provided a method of increasing Plutella xylostella mortality, comprising contacting a Plutella xylostella insect or insect population with a compound or composition or combinations as defined herein.

[0236] In one particular embodiment, there is provided a method of increasing Spodoptera frugiperda mortality, comprising contacting a Spodoptera frugiperda insect or insect population with a compound or composition as defined herein.

[0237] In one embodiment, there is provided a method of increasing dipteran insectmortality, comprising contacting a dipteran insect or dipteran insect population with a compound or composition or combinations of the invention.

[0238] In one particular embodiment, there is provided a method of increasing Drosophila suzukii mortality, comprising contacting a Drosophila suzukii insect or insect population with a compound or composition or combinations of the invention.

[0239] In one embodiment, there is provided a method of increasing hemipteran insect mortality, comprising contacting a hemipteran insect or hemipteran insect population with a compound or composition or combinations as defined herein.

[0240] In one 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 combinations as defined herein.

[0241] In one particular embodiment, there is provided a method of increasing Aphis fabae, Acyrthosiphon pisum, Myzus persicae, Amrasca biguttula or Rhopalosiphum padi mortality, comprising contacting an Aphis fabae, Acyrthosiphon pisum, Myzus persicae, Amrasca biguttula or Rhopalosiphum padi insect or insect population with a compound or composition or combinations as defined herein.

[0242] In one particular embodiment, there is provided a method of increasing Myzus persicae mortality, comprising contacting a Myzus persicae insect or insect population with a compound or composition or combinations as defined herein.

[0243] In one particular embodiment, there is provided a method of increasing Halyomorpha halys mortality, comprising contacting a Halyomorpha halys insect or insect population with a compound or composition or combinations as defined herein.

[0244] In one particular embodiment, there is provided a method of increasing Rhopalosiphum padi mortality, comprising contacting a Rhopalosiphum padi insect or insect population with a compound or composition or combinations as defined herein.

[0245] In one particular embodiment, there is provided a method of increasing Nilaparvata lugens mortality, comprising contacting a Nilaparvata lugens insect or insect population with a compound or composition or combinations as defined herein.

[0246] In one particular embodiment, there is provided a method of increasing Amrasca biguttula mortality, comprising contacting a Amrasca biguttula insect or insect population with a compound or composition or combinations as defined herein.

[0247] In one embodiment, there is provided a method of increasing coleopteran insect mortality, comprising contacting a coleopteran insect or coleopteran insect population with a compound or composition or combinations as defined herein.

[0248] In one embodiment, there is provided a method of increasing Blattodea insect mortality, comprising contacting a Blattodea insect or lepidopteran insect population with a compound or composition or combinations as defined herein.

[0249] In one particular embodiment, there is provided a method of increasing Blattella germanica mortality, comprising contacting a Blattella germanica insect or insect population with a compound or composition or combinations as defined herein. Methods of Inhibiting or Reducing infestation of a Plant or Site

[0250] The invention further provides a method of inhibiting infestation of a plant or plant part by insects, suitably by hemipteran, dipteran, lepidopteran, blattodea and / or coleopteran insects comprising contacting the plant or plant part with a compound, composition or combinations as described.

[0251] In one embodiment, there is provided a method of inhibiting infestation of a plant by lepidopteran insects comprising contacting the plant with a compound or composition or combinations as defined herein.

[0252] In one embodiment, there is provided a method of inhibiting infestation of a plant by Plutella xylostella comprising contacting the plant with a compound or composition or combinations as defined herein.

[0253] In one embodiment, there is provided a method of inhibiting infestation of a plant by Spodoptera frugiperda comprising contacting the plant with a compound or composition or combinations as defined herein.

[0254] In one embodiment, there is provided a method of inhibiting infestation of a plant by dipteran insects comprising contacting the plant with a compound or composition or combinations of the invention.

[0255] In one 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 combinations of the invention.

[0256] In one embodiment, there is provided a method of inhibiting infestation of a plant by hemipteran insects comprising contacting the plant with a compound or composition or combinations as defined herein.

[0257] In one embodiment, there is provided a method of inhibiting infestation of a plant by aphids comprising contacting the plant with a compound or composition or combinations as defined herein.

[0258] In one embodiment, there is provided a method of inhibiting infestation of a plant by Aphis fabae, Acyrthosiphon pisum, Myzus persicae, Amrasca biguttula or Rhopalosiphum padi comprising contacting the plant with a compound or composition or combinations as defined herein.

[0259] In one 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 combinations as defined herein.

[0260] 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 combinations as defined herein.

[0261] In one embodiment, there is provided a method of inhibiting infestation of a plant by Amrasca biguttula comprising contacting the plant with a compound or composition or combinations as defined herein.

[0262] In one embodiment, there is provided a method of inhibiting infestation of a plant by Nilaparvata lugens comprising contacting the plant with a compound or composition or combinations as defined herein.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 combinations as defined herein.

[0263] In one embodiment, there is provided a method of inhibiting infestation of a plant by coleopteran insects comprising contacting the plant with a compound or composition or combinations as defined herein.

[0264] The invention further provides a method of inhibiting infestation of a site on which plants are growing or intended to be grown by insects, suitably by hemipteran, dipteran, lepidopteran, blattodea and / or coleopteran insects comprising contacting the site with a compound, composition, or combinations as described.

[0265] The method may be prophylactic. Thus, for example, the compound may be applied to the plant or plant part, or site, while the plant or part or field is free or substantially free of insects.

[0266] Suitably the site may be any agricultural site suitable for growing plants. Suitably the site may be any area or locale which may be suitable for growing plants, or in which plants are grown. Suitable sites may include farmland, brownfield sites, fields, greenhouses, conservatories, containers, aquaponics and hydroponics systems etc. In one embodiment, the site is a field.

[0267] Alternatively, the plant or plant part or site may already be colonised or infested by insects, suitably by hemipteran, dipteran, lepidopteran, blattodea and / or coleopteran insects.

[0268] Thus, the invention further provides a method of reducing insect infestation of a plant or plant part, or of reducing insect load on a plant or plant part, the method comprising contacting the plant or plant part with a compound, composition, or combinations as described herein. The invention also provides a method of reducing insect infestation of a field, or of reducing an insect load in a field, the method comprising contacting the field with a compound, composition, or combinations as described herein. Suitably of hemipteran, dipteran, lepidopteran, blattodea and / or coleopteran insects. Methods of Decreasing Insect Feeding

[0269] The invention further provides a method of decreasing insect feeding, comprising contacting an insect or insect population with a compound, composition or combinations as described herein. Suitably decreasing insect feeding on a plant or plant part. The insect or insect population may be hemipteran, dipteran, lepidopteran, blattodea and / or coleopteran insects. Methods of Protecting a Plant from Insects

[0270] The invention further provides a method of protecting a plant or part thereof from insects, or from insect infestation, and specifically a method of protecting a plant or plant part against hemipteran, dipteran, lepidopteran, blattodea and / or coleopteran insects or infestation thereof, wherein the method comprises the step of applying directly or indirectly to the plant or to a part of the plant, an insecticidal compound or composition, or combinations of the invention. Suitably applying indirectly may comprise applying the compound or composition or combinations of the invention to the field or locale in which the plant is growing, or in which it is intended to be grown.

[0271] The present invention also provides post-harvest treatment methods for protecting or treating a harvested plant or a harvested part of the plant against insects, or insect infestation, specifically against hemipteran, dipteran, lepidopteran, blattodea and / or coleopteran insects or infestation thereof, the method comprising the step of applying directly or indirectly to the harvested plant or to a harvested part of the plant, an insecticidal compound or composition or combinations of the invention, under conditions effective to protect or treat the harvested plant or a harvested part of the plant against the insects. Suitably applying indirectly may comprise applying the compound or composition or combinations of the invention to the location in which the plant or a harvested part of the plant is stored, or in which it is intended to be stored.

[0272] Suitably the insect may be of the order hemipteran, dipteran, lepidopteran, blattodea and / or coleopteran. More suitably, the insect is of the order hemipteran, dipteran and / or lepidopteran. More suitably, the insect is of the order lepidoptera. Most suitably, the insect is Plutella xylostella or Spodoptera frugiperda.

[0273] Methods of Contacting an Insect

[0274] 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 to or on sites frequented by the insect a compound or composition or combinations according to the invention.

[0275] The site, frequented by insects may be a natural habitat for insects, or a place regularly visited by insects. This site can be treated then with the compound or composition as described above: as a non-limiting example mosquito nets, impregnated withencapsulated insecticide, can be used as application method. Alternatively, said site is created by application of a visual lure or of an attractant for the insects. Visual lures are known to the person skilled in the art, and include but are not limited to light sources, coloured object and shapes or silhouettes that stand out of a contrasting background. As mentioned above, insect attractants include but are not limited to pheromones, kairomones and allomones. The attractant may be present in the composition or it may be applied separately from the compound or composition or combinations, to ensure that the insects are attracted to the site where the compound or composition or combinations is applied.

[0276] Suitably the insect may be of the order hemipteran, dipteran, lepidopteran, blattodea and / or coleopteran. More suitably, the insect is of the order lepidoptera. More suitably, the insect is Plutella xylostella or Spodoptera frugiperda. Application of the Compounds or Compositions

[0277] The compound or composition or combinations of the invention may be contacted with the insect or insect population, suitably this may comprise applying the compound or composition or combinations directly to an insect or insect population. For example, it may be applied topically. Alternatively, the compound or composition or combinations may be applied indirectly. For example, it may be applied to a substrate, site, or locale likely to come into contact with an insect or insect population. The substrate may be a plant or plant part, especially for Hemiptera or Diptera or Coleoptera or Lepidoptera or Blattodea which represent pests of plants (whether crops or horticultural plants), or may be a field, locale, or area suitably in which the plants are grown. Suitably therefore the compound or composition or combinations may be applied to the plant or plant part. Suitably therefore the compound or composition or combinations may be applied to the site in which the plant is grown.

[0278] However, for insects which represent pests to humans, such as the Cimicidae family (e.g. bedbugs of the genus Cimex, such as Cimex lectularius) or the Reduviidae family (e.g. of the genus Rhodnius such as Rhodnius prolixus, or Triatoma such as Triatoma infestans) which can be vectors of human disease, the substrate may be a domestic surface or article, such as bedding, a mattress, or any other suitable domestic surface (e.g. wood). The compound or composition may be applied to the substrate in a form suitable for ingestion by an insect.

[0279] Suitably contacting may comprise feeding or spraying, for example. Suitably feeding may be encouraged via bait attractants, which may be comprised in a composition of the invention, as explained below.

[0280] The methods may comprise contacting or applying directly or indirectly to the plant or to a part of the plant a compound or composition or combinations as disclosed herein, for example at an application rate higher than 5g of the compound per hectare, suchas but not limited to an application rate higher than 10g of the compound per hectare, such as an application rate higher than 24g of the compound per hectare, such as an application rate higher than 50g of the compound per hectare, such as an application rate higher than 75g of the compound per hectare, such as an application rate higher than 100g of the compound per hectare, or in particular an application rate higher than 200g of the compound per hectare. These methods may comprise applying directly or indirectly to the plant or to a part of the plant a compound, composition or combinations as disclosed herein, for example at an application rate between 5g and 100g of the compound composition or combinations per hectare, such as but not limited to an application rate of between 5g and 200g of the compound composition or combinations per hectare, in particular an application rate of between 5g and 50g of the compound composition or combinations per hectare, such as between 5g and 30g of the compound composition or combinations per hectare or between 10g and 25g per hectare.

[0281] The compounds or compositions or combinations as disclosed herein may be directly or indirectly contacted with / applied to the plant or to a part of the plant by spraying, atomizing, foaming, fogging, culturing in hydroculture, culturing in hydroponics, coating, submerging, and / or encrusting, optionally post-harvest. Suitably contacting may comprise feeding or spraying, for example. In some embodiments, the contacting is by feeding.

[0282] Suitably the compound may be contacted with the insect or insect population, or plant or plant part, at any suitable concentration which is effective. Suitably the compositions and combinations may comprise such an effective concentration of a compound. Suitably the concentration of the compound is between 10-3to 10-9M, suitably between 10-4to 10-6M, suitably between 10-4to 10-5M. Use as a Plant Protection Agent

[0283] The invention further provides the use of a compound, composition or combination as described herein as a plant protection agent, and specifically for protecting a plant or plant part against insects, suitably against hemipteran, dipteran and / or lepidopteran insects. Plant protection agents are described further hereinabove. Use as an Insect Control Agent

[0284] The present invention provides the use of a compound or composition or combination thereof as described herein as an insect control agent, specifically in methods of increasing mortality in insects, or a method of inhibiting infestation of a plant by insects.

[0285] The present invention also provides the use of a compound or composition or combination thereof as described herein as an insect control agent, specifically in methods of increasing hemipteran, dipteran, lepidopteran, blattodea and / or coleopteran insect mortality, or in a method of inhibiting or reducing infestation, or reducing insect load of a plant by insects, suitably by hemipteran, dipteran, lepidopteran, blattodea and / or coleopteraninsects.

[0286] The present invention also provides the use of a compound or composition or combination thereof as described herein as an insect control agent, specifically by having a biostatic effect on hemipteran, dipteran, coleopteran and / or lepidopteran insects, a biocidal effect on hemipteran, dipteran, coleopteran and / or lepidopteran insect, and / or a pesticidal effect hemipteran, dipteran, coleopteran and / or lepidopteran insect.

[0287] “Biostatic (effect)” or “biostatic use”, as used herein, includes any effect or use of a compound or composition or combination as described herein (optionally comprised in a biostatic, biocidal, fungicidal or fungistatic composition as defined herein) for controlling, modulating or interfering with the harmful activity of a pest, such as a plant pest or a plant pathogen. Suitably the pest is of hemipteran, dipteran, lepidopteran, blattodea and / or coleopteran insect orders. Suitably including but not limited to inhibiting the growth or activity of the insect, altering the behaviour of the insect, and repelling or attracting the insect in plants, plant parts or in other agro-related settings, such as for example for household uses or in soil.

[0288] “Pesticidal activity” or “biocidal activity”, as used interchangeably herein, means killing the pest or severely disabling the pest. Suitably which may be the same as insecticidal activity wherein the pest is an insect. Suitably, the compound, composition or combination may be for use as an insect control agent wherein the insect encodes an AKH and / or a kinin peptide.

[0289] Suitably, the compound composition or combination may be for use as an insect control agent wherein the insect is of the order dipteran. Suitably, the compound may be for use as an insect control agent wherein the insect is of the genus Drosophila. Suitably, the compound may be for use as an insect control agent wherein the insect is Drosophila suzukii.

[0290] Suitably, the compound or composition or combination as defined herein may be for use as an insect control agent wherein the insect is of the order hemipteran. Suitably, the compound or composition or combination as defined herein may be for use as an insect control agent wherein the insect is an aphid. Suitably, the compound or composition or combination as defined herein may be for use 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 for use as an insect control agent wherein the insect is Myzus persicae.

[0291] Suitably, the compound or composition or combination as defined herein may be for use as an insect control agent wherein the insect is of the order hemipteran. Suitably, the compound or composition or combination as defined herein may be for use 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 for use as an insect control agentwherein the insect is Halyomorpha halys.

[0292] Suitably, the compound or composition as defined herein may be for use as an insect control agent wherein the insect is of the family Cicadellidae. Suitably, the compound or composition as defined herein may be for use as an insect control agent wherein the insect is Amrasca biguttula.

[0293] Suitably, the compound or composition or combination as defined herein may be for use as an insect control agent wherein the insect is of the order lepidopteran. Suitably, the compound or composition or combination as defined herein may be for use 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 for use as an insect control agent wherein the insect is Plutella xylostella.

[0294] Suitably, the compound or composition or combination as defined herein may be for use as an insect control agent wherein the insect is of the genus Spodoptera. Suitably, the compound or composition or combination as defined herein may be for use as an insect control agent wherein the insect is Spodoptera frugiperda.

[0295] Suitably, the compound or composition or combination as defined herein may be for use as an insect control agent wherein the insect is of the order coleopteran.

[0296] Suitably, the compound or composition or combination as defined herein may be for use as an insect control agent wherein the insect is of the order Blattodea. Suitably, the compound or composition or combination as defined herein may be for use as an insect control agent wherein the insect is a cockroach or a termite. Methods of controlling Insect Fecundity

[0297] The present invention also provides insecticidal compounds, compositions and combinations as described herein for controlling fecundity of insect species. Suitably, the insect is selected from hemipteran, dipteran, lepidopteran, blattodea and / or coleopteran insects, such as those described anywhere herein. More suitably, the insect is a lepidopteran insect, for example Plutella xylostella.

[0298] There is also provided a method of controlling fecundity of an hemipteran insect, the method comprising contacting a compound of the invention, or a composition of the invention to a substrate, e.g. a plant or soil. Suitably, the hemipteran insect is any of those disclosed herein, e.g., an aphid.

[0299] There is also provided a method of controlling fecundity of a dipteran insect, the method comprising contacting a compound of the invention, or a composition of the invention to a substrate, e.g. a plant or soil. Suitably, the dipteran insect is any of those disclosed herein.

[0300] There is also provided a method of controlling fecundity of an lepidopteran insect, the method comprising contacting a compound of the invention, or a composition ofthe invention to a substrate, e.g. a plant or soil. Suitably, the lepidopteran insect is any of those disclosed herein. Most suitably, the insect is Plutella xylostella or Spodoptera frugiperda.

[0301] There is also provided a method of controlling fecundity of an coleopteran insect, the method comprising contacting a compound of the invention, or a composition of the invention to a substrate, e.g. a plant or soil. Suitably, the coleopteran insect is any of those disclosed herein.

[0302] There is also provided a method of controlling fecundity of a blattodea insect, the method comprising contacting a compound of the invention, or a composition of the invention to a substrate, e.g. a plant or soil. Suitably, the blattodea insect is any of those disclosed herein.

[0303] There is also provided a method of controlling fecundity of a hemipteran insect, the method comprising contacting a combination as described herein, to a substrate, e.g. a plant or soil. 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.

[0304] There is also provided a method of controlling fecundity of a dipteran insect, the method comprising contacting a combination as described herein, to a substrate, e.g. a plant or soil. 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.

[0305] There is also provided a method of controlling fecundity of a lepidopteran insect, the method comprising contacting a combination as described herein, or a composition of the invention to a substrate, e.g. a plant or soil. Suitably, the lepidopteran insect is any of those disclosed herein. Suitably, the combination comprises a compound of the invention, and a kinin peptide, or an analogue thereof.

[0306] There is also provided a method of controlling fecundity of a coleopteran insect, the method comprising contacting a combination as described herein, or a composition of the invention to a substrate, e.g. a plant or soil. Suitably, the coleopteran insect is any of those disclosed herein. Suitably, the combination comprises a compound of the invention, and a kinin peptide, or an analogue thereof.

[0307] There is also provided a method of controlling fecundity of a blattodea insect, the method comprising contacting a combination as described herein, or a composition of the invention to a substrate, e.g. a plant or soil. Suitably, the blattodea insect is any of those disclosed herein. Suitably, the combination comprises a compound of the invention, and a kinin peptide, or an analogue thereof.

[0308] There is also provided a method of controlling fecundity of an hemipteraninsect or insect population, the method comprising contacting a compound of the invention, or a composition of the invention to an hemipteran insect or insect population. Suitably, the hemipteran insect is any of those disclosed herein.

[0309] There is also provided a method of controlling fecundity of a dipteran insect or insect population, the method comprising contacting a compound of the invention, or a composition of the invention to a dipteran insect or insect population. Suitably, the dipteran insect is any of those disclosed herein.

[0310] There is also provided a method of controlling fecundity of a lepidopteran insect or insect population, the method comprising contacting a compound of the invention, or a composition of the invention to a lepidopteran insect or insect population. Suitably, the lepidopteran insect is any of those disclosed herein. Most suitably, the insect is Plutella xylostella or Spodoptera frugiperda.

[0311] There is also provided a method of controlling fecundity of a coleopteran insect or insect population, the method comprising contacting a compound of the invention, or a composition of the invention to a coleopteran insect or insect population. Suitably, the coleopteran insect is any of those disclosed herein.

[0312] There is also provided a method of controlling fecundity of a blattodea insect or insect population, the method comprising contacting a compound of the invention, or a composition of the invention to a blattodea insect or insect population. Suitably, the blattodea insect is any of those disclosed herein.

[0313] There is also provided a method of controlling fecundity of a hemipteran insect or insect population, the method comprising contacting a combination as described herein, to a hemipteran insect or insect population. 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.

[0314] There is also provided a method of controlling fecundity of a dipteran insect or insect population, the method comprising contacting a combination as described herein, to a dipteran insect or insect population. 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.

[0315] There is also provided a method of controlling fecundity of a lepidopteran insect or insect population, the method comprising contacting a combination as described herein, or a composition of the invention to a lepidopteran insect or insect population. Suitably, the lepidopteran insect is any of those disclosed herein. Suitably, the combination comprises a compound of the invention, and a kinin peptide, or an analogue thereof.

[0316] There is also provided a method of controlling fecundity of a coleopteran insect or insect population, the method comprising contacting a combination as describedherein, or a composition of the invention to a coleopteran insect or insect population. Suitably, the coleopteran insect is any of those disclosed herein. Suitably, the combination comprises a compound of the invention, and a kinin peptide, or an analogue thereof.

[0317] In the context of the present invention, "controlling fecundity" refers to reducing, inhibiting, or eliminating the presence of an insect species during one or more of its growth stages. For example, the compositions of the present invention may be used for controlling the growth of mites at any stage such as egg, larva, nymph, and adult form. Combinations with Further Insecticides

[0318] The compound of the invention may be used in combination with one or more further insecticides, such as those as described herein. There is also provided a combination comprising a compound of the invention, or a salt or solvate thereof, in combination with one or more additional active insecticides, or insecticidal compounds.

[0319] The composition of the invention may further comprise one or more additional active insecticides, or active insecticidal compounds.

[0320] Suitably, the insecticide may be selected from an insect neuropeptide or analogues thereof such as a kinin peptide, a AKH peptide, a DH31 peptide, a DH44 peptide, a pyrokinin peptide or a CAPA peptide (e.g. a CAPA-1, CAPA-2 or CAPA-3 peptide or analogue).

[0321] Additionally or alternatively, the insecticide may be selected from a chemical insecticide, such as: Pyrethroids (Permethrin, Cypermethrin, Deltamethrin); Organophosphates (Malathion, Chlorpyrifos, Diazinon); Neonicotinoids (Imidacloprid, Clothianidin, Thiamethoxam); Carbamates (Carbaryl, Methomyl, Propoxur); Botanical Insecticides (Pyrethrin (derived from chrysanthemum flowers), Rotenone (derived from certain plant roots)); Biopesticides (Bacillus thuringiensis (Bt) products, Beauveria bassiana (fungus), Metarhizium anisopliae (fungus)); Insect Growth Regulators (IGRs) (Methoprene, Pyriproxyfen); Fipronil; Spinosad; Avermectins (including abamectin and ivermectin); Chitin Synthesis Inhibitors (Diflubenzuron, Hexaflumuron); Piperonyl Butoxide; Flonicamid; Indoxacarb; dichlorodiphenyltrichloroethane; and Sulfoxaflor.

[0322] In a particular embodiment, the further insecticide is a kinin peptide, for example SB-P-69 (Hy-NFSPWG-[NH2], SEQ ID NO: 55).

[0323] In a particular embodiment, the further insecticide is an AKH peptide.

[0324] In a particular embodiment, the further insecticide is a DH31 peptide.

[0325] In a particular embodiment, the further insecticide is a DH44 peptide,

[0326] In a particular embodiment, the further insecticide is a pyrokinin peptide, for example SB-P-048 (EQNVQSNGEPAYRVRTPRL-[NH2], SEQ ID NO: 34), SB-P-49 ([Hy]- SVPFKPRL-[NH2], SEQ ID NO: 35), SB-P-51 ([Hy]-LRQLQSNGEPAYRVRTPRL-[NH2] , SEQ ID NO: 36),

[0327] In a particular embodiment, the further insecticide is a CAPA peptide (e.g. a CAPA-1, CAPA-2 or CAPA-3 peptide or analogue).

[0328] Suitably said further insecticides or insecticidal compounds may be comprised in a composition of the invention.

[0329] The methods of the invention may further comprise contacting the insect population or plant or part thereof with a further insecticide agent, or insecticidal compound, such as those described herein. Suitably, the further insecticide or insecticidal compound is a kinin peptide.

[0330] Suitably any references herein to the compound of the invention or a composition thereof may equally refer to a combination of a compound of the invention with one or more insecticides or insecticidal compounds, or a composition containing such a combination.

[0331] In a particular embodiment, where the peptides of the invention are to be used as insecticides against insects of the order Dipteran (e.g. D. suzukii), then they may be utilised in combination with an AKH peptide, a kinin peptide and / or a pyrokinin peptide, or a modified analogue thereof.

[0332] In a particular embodiment, where the peptides of the invention are to be used as insecticides against insects of the order Hemipteran (e.g. M. persicae), then they may be utilised in combination with a kinin peptide and / or a pyrokinin peptide, or a modified analogue thereof.

[0333] In a particular embodiment, where the peptides of the invention are to be used as insecticides against insects of the order Lepidopteran (e.g. P. xylostella), then they may be utilised in combination with a kinin peptide, a CAPA peptide and / or a pyrokinin peptide, or a modified analogue thereof.

[0334] The choice of ancillary or additional insecticides will typically depend on the particular target species. Beneficial Insect Species

[0335] The compounds, compositions and combinations of the invention may be substantially non-toxic to beneficial insect species, including species which prey on pests and pollinator species. Important pollinator species, such as insects of the superfamily Apoidea, including bees, such as the Apidae, e.g. those of the genus Bombus, such as Bombus terrestris. Important predatory species include Coccinellidae (lady bugs) such as Adalia bipunctata.

[0336] By substantially non-toxic, it is meant that the compounds, compositions and combinations of the invention do not cause death of the beneficial insect species (e.g. pollinator species), suitably that they do not cause premature death of the beneficial insect species (e.g. pollinator species). It is also meant that the compounds, compositions andcombinations of the invention do not cause any detrimental side effects to the beneficial insect species (e.g. pollinator species), for example they do not have a negative effect on feeding behaviour, or ability to move. Compositions

[0337] The present inventors have provided compositions comprising at least one insecticidal compound or combination thereof of the invention, which can specifically bind to an insect. Importantly, through this interaction with a specific molecular structure of the insect, such as a receptor, suitably a neurological receptor, the compositions disclosed herein are capable of inhibiting, preventing or reducing one or more biological activities of the insect, such that the growth or fecundity of the insect is inhibited, prevented or reduced. In certain embodiments, the compositions as disclosed herein are capable of killing insects through the specific interaction of at least one insecticidal compound, which can specifically bind to an insect receptor, and which is comprised in the compositions.

[0338] Compositions of the invention, or for use in accordance with the invention, typically comprise a compound as described in combination with one or more ancillary component such as solvents, carriers, diluents, adjuvants, preservatives, dispersants, emulsifying agents, or synergists.

[0339] Suitably the composition may be an agricultural composition, an insect control composition (e.g. insecticide composition), or a plant protection composition.

[0340] In any of these embodiments, the compound or 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. insecticide composition) or a plant protection composition. Reference to application or use of a compound or combination herein should therefore be construed as encompassing application or use of a suitable composition thereof, unless the context demands otherwise.

[0341] The composition typically comprises a compound as described herein in admixture with one or more ancillary component such as solvents, carriers, diluents, adjuvants, preservatives, dispersants, emulsifying agents, or synergists.

[0342] The composition may further comprise a combination with one or more additional active insecticides as described herein.

[0343] The invention further provides a composition, e.g. an agricultural composition, an insect control composition or plant protection composition, comprising a compound of the invention, or a combination thereof, in admixture with one or more solvents, carriers, diluents, adjuvants, preservatives, dispersants, emulsifying agents, or synergists. The composition may be an aqueous composition. Further details of which are explained hereinbelow.

[0344] “Agricultural”, as used herein, means suitable for use in the agricultural oragrochemical industry, including horticulture, floriculture and home and garden uses, but also products intended for non-crop related uses such as public health / pest control operator uses to control undesirable insects and rodents, household uses, such as household fungicides and insecticides and agents, for protecting plants or parts of plants, crops, bulbs, tubers, fruits (e.g. from harmful organisms, diseases or pests); for controlling, preferably promoting or increasing, the growth of plants; and / or for promoting the yield of plants, crops or the parts of plants that are harvested (e.g. its fruits, flowers, seeds etc.). Examples of such substances will be clear to the skilled person and preferably in the context of the present invention, include compounds that are active as insecticides (e.g. contact insecticides or systemic insecticides, including insecticides for household use). Other such agrochemicals may be pesticides, growth regulators, nutrients / fertilizers, repellants, defoliants etc.

[0345] “Agricultural use”, as used herein, not only includes the use of the insecticidal compounds of the invention, combinations thereof or compositions, and optionally the agrochemicals as defined above (for example, pesticides, growth regulators, nutrients / fertilizers, repellants, defoliants etc.), that are suitable and / or intended for use in field grown crops (e.g., agriculture), but also includes the use of compounds of the invention combinations thereof or compositions and said agrochemicals as defined above that are meant for use in greenhouse grown crops (e.g. horticulture / floriculture) or hydroponic culture systems and even the use of compounds combinations thereof or compositions of the invention and agrochemicals as defined above that are suitable and / or intended for non-crop uses such as uses in private gardens, household uses (for example, herbicides or insecticides for household use), or uses by pest control operators (for example, weed control etc.).

[0346] Suitably an insect control composition according to the invention is for controlling insect populations. Formulations of such compositions for controlling insect populations are known to the person skilled in the art and include, but are not limited to liquid emulsifiable concentrates, wettable powders, solutions, suspension concentrates, emulsions, suspoemulsions, granules and water dispersible granules (Mulqueen, 2003). Preferably, said insect control compositions according to the invention comprise an insecticidal compound of the invention, and optionally a combination of further insecticidal compounds. Suitably said insecticidal compound is comprised in a carrier as described hereinbelow.

[0347] Compositions of the invention may comprise a pesticide formulation or an agrochemical formulation. A "pesticide formulation" as used herein means any composition comprising a compound or combination of compounds intended for preventing, destroying, repelling, attracting or mitigating any pest. An "agrochemical formulation" as used hereinmeans a composition for agricultural use, comprising a biologically active agent, optionally with one or more additives favouring optimal dispersion, atomization, distribution, retention and / or activity of agrochemicals. As a non-limiting example such additives are diluents, solvents, adjuvants, surfactants, wetting agents, spreading agents, oils, stickers, penetrants, buffering agents, acidifiers, defoaming agents or drift control agents.

[0348] A composition as used herein means a composition comprising at least one active substance, suitably an insecticidal compound of the invention, optionally with one or more additives favouring optimal dispersion, atomization, deposition, leaf wetting, distribution, retention and / or uptake of said active substance. It will become clear from the further description herein that a composition as used herein includes biological insect control agents or biological insecticides, and these terms will be interchangeably used in the present application. Accordingly, a composition as used herein includes compositions comprising at least one biological molecule as an active ingredient, substance or principle for controlling pests in plants or in other agro-related settings (such for example in soil). Suitably wherein the at least one biological molecule comprises an insecticidal compound of the invention or a combination thereof. Suitably wherein the pest is an insect. As a non-limiting example, the additives in the compositions disclosed herein may include but are not limited to diluents, solvents, adjuvants, surfactants, wetting agents, spreading agents, oils, stickers, thickeners, penetrants, buffering agents, acidifiers, antisettling agents, anti-freeze agents, photo- protectors, defoaming agents, biocides and / or drift control agents.

[0349] Suitably, the compositions of the invention are aqueous compositions.

[0350] The compound content of the composition can vary within wide limits. The compound concentration of the composition is suitably an effective amount, and can be from 0.0000001 to 95% by weight of the compound, preferably between 0.0001 and 1% by weight. The terms "effective amount" and "effective dose", as used herein, mean the amount needed to achieve the desired result or results.

[0351] In a specific embodiment the concentration of the compound of the invention contained in the composition may be at least 0.0001% by weight. In a specific embodiment the concentration of the compound of the invention contained in the composition may be up to 50% by weight. In a specific embodiment the concentration of the compound of the invention contained in the composition may be from 0.0001% to 50% by weight. In particular embodiments, the present invention provides compositions comprising at least one insecticidal compound of the invention, wherein the concentration of the at least one compound of the 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 invention contained in the composition may be from 0.001 % to 50% by weight. In yet another specific embodiment the concentration of the at least one compound of the invention contained inthe composition may be from 0.01% to 50% by weight. In yet another specific embodiment the concentration of the at least one compound of the invention contained in the composition may be from 0.1% to 50% by weight.

[0352] The compositions of the invention, or for use in accordance with the invention, may comprise more than one compound of the invention in combination, and / or with other insecticidal compounds as described herein in combination. Therefore, the compositions of the invention may comprise a first compound of the invention and a second compound of the invention, or a first compound of the invention and a second insecticidal compound, for example. Suitably the first and second compound may be any of those described herein, and may be present in the composition in any relative proportion.

[0353] The composition may be an aqueous composition, e.g. a saline composition. The aqueous composition may contain one or more buffers, such as a phosphate buffer (e.g. phosphate buffered saline) or a Tris buffer. Alternatively, the composition may be an oil dispersion or an emulsion, e.g. an oil and water emulsion. Alternatively the composition may be a suspension, powder, foam, paste, granule, aerosol, impregnated natural and synthetic substance, or encapsulated in polymeric substance for example. A suitable form of the composition may be chosen for the intended use having regard to the target insect, and to its habitat.

[0354] Adjuvants may enhance product performance, for example, by increasing the efficiency of the delivery of active ingredients, reducing the level of active ingredient required, or extending the spectrum of effectiveness.

[0355] Different types of adjuvants offer various benefits and advantages, which are achieved by modulating properties such as spray formation, spray retention, wetting, deposit formation or uptake.

[0356] Adjuvants modulating spray formation may influence spray quality by reducing spray drift and wastage, allowing more of the product to reach the target. This can reduce use rates, leading to a better environmental profile and a potentially more cost effective solution. Such adjuvants include non-ionic surfactants and emulsifier blends.

[0357] Adjuvants modulating spray retention may dissipate the kinetic energy of the droplet during impact, meaning the likelihood of bounce or run-off is reduced. Such adjuvants include alkyl polyglucosides, alkoxylated alcohols, and polyoxyethylene monobranched alcohols (e.g. polyoxyethylene (8) monobranched alcohol).

[0358] Adjuvants modulating wetting properties (i.e. wetting agents) may reduce surface tension and contact angle, leading to enhanced coverage. Such adjuvants include polyoxyethylene sorbitan monolaurate (e.g. polyoxyethylene (8) sorbitan monolaurate), surfactant blends, and alkyl polyglucosides.

[0359] Adjuvants modulating deposit formation may influence evaporation of waterfrom the droplet and thus provide a more homogeneous distribution. Such adjuvants include alkoxylated polyol esters, polyoxyethylene sorbitan monolaurate (e.g. polyoxyethylene (12) sorbitan monolaurate), and alkyl polyglucoside.

[0360] Adjuvants modulating uptake can improve penetration and uptake of active ingredients. e.g. through the insect cuticle, 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).

[0361] Dispersants may be aqueous or non-aqueous. An oil dispersion (OD) formulation typically comprises a solid active ingredient dispersed in oil. The oil can vary from paraffinic to aromatic solvent types and vegetable oil or methylated seed oils. Typically, the active ingredient is uniformly suspended in the oil phase. Although primarily used for water sensitive active ingredients, OD formulations have extended to other active ingredients due to their better spray retention, spreading, foliar uptake, and penetration enhancement (e.g. across the insect cuticle) as the carrier oil often acts as an adjuvant.

[0362] Oils suitable for use in OD dispersions include linseed, rapeseed and soyabean oils.

[0363] Aqueous dispersants may be used, for example, to improve stability in the spray tank after dilution in water, and may include modified styrene acrylic polymers, and polymeric amphoteric dispersants and adjuvants.

[0364] An emulsifier may be employed to emulsify a continuous oil phase into water when an OD formulation is diluted prior to being sprayed. The emulsifier may be selected based upon its ability to spontaneously form the emulsion. Their performance is primarily dictated by the nature of the surfactant and their collective effect on how they arrange themselves at the oil / water interface. Examples include polyoxyethylene sorbitol hexaoleate (e.g. polyoxyethylene (40) sorbitol hexaoleate), emulsifier blends, and calcium alkylaryl sulphonate.

[0365] The composition may further comprise an adhesive or a dye.

[0366] The compound may be provided in the form of a concentrate, for dilution prior to application. Alternatively the compound may be provided in a solid form to be suspended or dissolved prior to formulation.

[0367] The compositions as disclosed herein are themselves in fairly diverse, solid or liquid, forms. As solid composition forms, there may be mentioned dustable powders (content of active substance which may be up to 100%) and granules, in particular those obtained by extrusion, by compacting, by impregnation of a granulated carrier, by granulation using a powder as starting material (the content of active substance in these granules being between 0.5 and 80% for these latter cases). Such solid compositions may be optionally used in the form of a liquid which is viscous to a greater or lesser degree,depending on the type of application desired, for example by diluting in water. As liquid composition forms or forms intended to constitute liquid compositions during application, there may be mentioned solutions, in particular water-soluble concentrates, emulsions, suspension concentrates, wettable powders (or spraying powder), oils and waxes. The suspension concentrates, which can be applied by spraying, are prepared so as to obtain a stable fluid product which does not form a deposit and they usually contain from 10 to 75% of active substance, from 0.5 to 15% of surfactants, from 0.1 to 10% of thixotropic agents, from 0 to 10% of appropriate 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 or not very soluble: some organic solids or inorganic salts may be dissolved in the carrier to help prevent sedimentation or as antigels for water.

[0368] A “carrier”, as used herein, means any solid, semi-solid or liquid carrier in or on(to) which an active substance, such as the insecticidal compounds or combinations of the invention, can be suitably incorporated, included, immobilized, adsorbed, absorbed, bound, encapsulated, embedded, attached, or comprised. Non-limiting examples of such carriers include nanocapsules, microcapsules, nanospheres, microspheres, nanoparticles, microparticles, liposomes, vesicles, beads, a gel, weak ionic resin particles, liposomes, cochleate delivery vehicles, small granules, granulates, nano-tubes, bucky-balls, water droplets that are part of an 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 shells, 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 even microbial cells (such as yeast cells) or suitable fractions or fragments thereof.

[0369] In one embodiment, the carrier is a liposome. In one embodiment, the composition of the invention comprises one more liposomes suitably wherein each liposome comprises a compound of the invention, or 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 liposomes comprise a lipid component, suitably which may be soy lecithin and glycerol. Suitably the liposomes are formed of soy lecithin and glycerol. Suitably the liposomes are formed of 25mg / ml of glycerol and 3% glycerol. Suitably the liposomes comprise an effective concentration of the compound of the invention. Suitably the liposomes comprise around 10-4M of 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 25mg / ml) and glycerol (preferably 3%).

[0370] Suitably the liposomes may be manufactured by the Mozafari Heating Method (Mozafari, M. R. "Nanoliposomes: preparation and analysis." Liposomes: Methods and Protocols, Volume 1: Pharmaceutical Nanocarriers (2010): 29-50. Suitably such a method comprises (a) admixing the compound of the invention with glycerol, suitably with a 50% glycerol solution, (b) admixing the mixture of step (a) with soy lecithin, suitably with 350 mg of soy lecithin in an aqueous solution, (c) heating the mixture of step (b) whilst stirring to form liposomes, suitably at around 60°C and at around 800RPM for around 40 minutes, (d) annealing the liposomes, suitably by placing in 40C water for around 1-2 hours, and (e) sonicating the liposomes, suitably for around 30 minutes in a sonicator bath.

[0371] Suitably the liposomes have an average diameter of around 150 to 250nm, suitably around 175nm to 225nm, suitably around 190nm to 210nm, suitably around 200nm. Suitably the size of the liposomes is determined by using Dynamic light scattering (DLS), for example using a Malvern Zetasizer Nano. Suitably the liposomes have a polydispersity index of between 0.25 to 0.35, suitably 0.26 to 0.33, suitably 0.26 to 0.31, suitably 0.26 to 0.30, suitably 0.26 to 0.29, suitably 0.26 to 0.28, suitably around 0.26.

[0372] In the compositions of the invention, the carrier with the one or more insecticidal compounds may for example be maintained as a wettable powder, wettable granule, emulsifiable concentrate, suspension concentrate, microemulsion, capsule suspension, dry microcapsule, tablet or gel or be suspended, dispersed, emulsified or otherwise brought in a suitable liquid medium (such as water or another suitable aqueous, organic or oily medium) so as to provide a (concentrated) liquid composition of the invention that has a stability that allows the composition of the invention to be suitably stored or (where necessary after further dilution) applied to the intended site of action. Suitably the composition of the invention can be transported and / or stored prior to final use, optionally (and usually preferably) as a suitable liquid concentrate, dry powder, tablet, capsule suspension, slurry or "wet cake", which can be suitably diluted, dispersed, suspended, emulsified or otherwise suitably reconstituted by the end user prior to final use. The composition of the invention allows to be applied to the intended site of action using any suitable or desired manual or mechanical technique such as spraying, pouring, dripping, brushing, coating, dripcoating, applying as small droplets, a mist or an aerosol or any other suitable technique. In one embodiment, said intended site of action is an intact living insect, even more preferably an insect surface.

[0373] The composition may be a bait composition for ingestion by the target insect. A bait composition may comprise one or more phagostimulants, i.e. a substance which will entice the insect to ingest the compound. Phagostimulants may include artificial sweeteners, amino acids, other peptides or proteins and carbohydrates (e.g. glucose, fructose, sucrose, maltose) etc. Examples include honey, syrups and aqueous solutions ofsucrose.

[0374] Commercially available base formulations may also be suitable for use in formulating the compounds described in this specification, such as Armid®FMPC (Akzo Nobel).

[0375] The composition may comprise one or more synergists, i.e. compounds which increase the efficacy of insecticides against their targets, often by inhibiting an insect’s ability to metabolise the active agent. Common synergists include piperonyl butoxide and MGK- 264 (n-octyl bicycloheptane dicarboximide), or peptidase inhibitors.

[0376] The composition may comprise one or more agents which promote stability of the insecticidal compounds of the invention. Suitably the one or more agents which promote stability may prevent degradation of the insecticidal compounds of the invention. Suitable agents which prevent degradation of the insecticidal compounds of the invention may inhibit or reduce the activity of enzymes, suitably of enzymes which act to degrade proteins, suitably proteases, for example. Suitably therefore the composition may comprise one or more protease inhibitors, suitably which may be selected from: Bowman-Birk Inhibitors, Kunitz Inhibitors, Cystatin, Trypsin Inhibitors, Serpins, Tannins, Proteinase Inhibitor-II (PI-II), and Alpha-AI1.

[0377] The composition may further comprise one or more additional, attractants, sterilizing agents, acaricides, nematicides, fungicides, growth-regulating substances or herbicides.

[0378] In some embodiments, the compositions may comprise one or more further agricultural chemicals or agrochemicals such as herbicides (e.g. contact herbicides or systemic herbicides, including herbicides for household use), fungicides (e.g. contact fungicides or systemic fungicides, including fungicides for household use), nematicides (e.g. contact nematicides or systemic nematicides, including nematicides for household use) and other pesticides or biocides (for example agents for killing insects or snails); as well as fertilizers; growth regulators such as plant hormones; micro-nutrients, safeners, pheromones; repellants; insect baits; and / or active principles that are used to modulate (i.e. increase, decrease, inhibit, enhance and / or trigger) gene expression (and / or other biological or biochemical processes) in or by the targeted plant (e.g. the plant to be protected or the plant to be controlled), such as nucleic acids (e.g., single stranded or double stranded RNA, as for example used in the context of RNAi technology) and other factors, proteins, chemicals, etc. known per se for this purpose, etc.

[0379] Examples of such agrochemicals will be clear to the skilled person; and for example include, without limitation: chlorantraniliprole, glyphosate, paraquat, metolachlor, acetochlor, mesotrione, 2,4-D,atrazine, glufosinate, sulfosate, fenoxaprop, pendimethalin, picloram, trifluralin, bromoxynil, clodinafop, fluroxypyr, nicosulfuron, bensulfuron, imazetapyr,dicamba, imidacloprid, thiamethoxam, fipronil, chlorpyrifos, deltamethrin, lambda-cyhalotrin, endosulfan, methamidophos, carbofuran, 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, sulphur, boscalid and other known agrochemicals or any suitable combination(s) thereof. Methods of Producing the Insecticidal Compounds

[0380] The insecticidal compounds described herein may be produced by any method known in the art for the production of peptides. In one embodiment, the insecticidal compounds may be produced by a chemical method, suitably a chemical synthesis method.

[0381] Any suitable chemical method may be used to synthesis the insecticidal compounds of the invention.

[0382] Suitably the insecticidal compounds are peptides. Suitably therefore they are synthesised by solid-state peptide synthesis. Suitably such synthesis may be carried out by using commercially available machines such as the Biotage Initiator+ Alstra microwave- assisted peptide synthesiser or the CEM Liberty Prime microwave-assisted peptide synthesiser.

[0383] In a further aspect of the invention, there is provided an isolated insecticidal compound produced by a process of the invention. Suitably an isolated insecticidal compound of formula (I) produced by a process of the invention.

[0384] In a further aspect of the invention there is provided a method of producing a composition as disclosed herein, at least comprising the steps of: (a) obtaining at least one insecticidal compound of formula (I); and (b) formulating the insecticidal compound into a composition.

[0385] In a further aspect of the invention, there is provided a method of producing and / or manufacturing a variant of the insecticidal compound of formula (I). Such may comprise the steps of: (i) modifying the peptide X-Y-Z of formula (I) by adding, replacing or deleting at least one amino acid; (ii) assessing the so created variant for 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 stable formulations), producibility, and production costs. Where the insecticidal activity is reduced in comparison to the unmodified peptide X-Y-Z, repeating the process of steps (i) and (ii) until a variant with improved insecticidal activity is obtained. Where the insecticidal activity is improved in comparison to the unmodified peptide X-Y-Z, the method may include further steps of manufacturing, isolating and purifying the variant. Screening for insecticidal activity and the other above described properties can be conducted as described below or generallyknown to the person skilled in the art.

[0386] In one embodiment is provided a method for manufacturing a variant of the insecticidal compound of the invention, comprising the steps of: a) modifying the peptide X-Y-Z by adding, replacing or deleting at least one amino acid; b) assessing the ability of the variant for 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 stable formulations), producibility, and production costs; c) where the insecticidal activity is reduced in comparison to the insecticidal compound comprising the unmodified peptide X-Y-Z, repeating the process of steps (a) and (b) until a variant with improved insecticidal activity is obtained; d) where the insecticidal activity is improved in comparison to the insecticidal compound comprising the unmodified peptide X-Y-Z, further manufacturing, isolating and purifying the variant.

[0387] Suitably the step of obtaining at least one insecticidal compound comprises (a) chemically synthesising the insecticidal compound.

[0388] Suitable compositions are described hereinabove. Suitable manufacturing methods for formulating the composition are known in the art and include, but are not limited to, high or low shear mixing, wet or dry milling, drip-casting, encapsulating, emulsifying, coating, encrusting, pilling, extrusion granulation, fluid bed granulation, co-extrusion, spray drying, spray chilling, atomization, addition or condensation polymerization, interfacial polymerization, in situ polymerization, coacervation, spray encapsulation, cooling melted dispersions, solvent evaporation, phase separation, solvent extraction, sol-gel polymerization, fluid bed coating, pan coating, melting, passive or active absorption or adsorption.

[0389] The features disclosed in the foregoing description, or in the following claims, or in the accompanying drawings, expressed in their specific forms or in terms of a means for performing the disclosed function, or a method or process for obtaining the disclosed results, as appropriate, may, separately, or in any combination of such features, be utilised for realising the invention in diverse forms thereof.

[0390] While the invention has been described in conjunction with the exemplary embodiments described above, many equivalent modifications and variations will be apparent to those skilled in the art when given this disclosure. Accordingly, the exemplary embodiments of the invention set forth above are considered to be illustrative and not limiting. Various changes to the described embodiments may be made without departing from the spirit and scope of the invention.

[0391] For the avoidance of any doubt, any theoretical explanations provided hereinare provided for the purposes of improving the understanding of a reader. The inventors do not wish to be bound by any of these theoretical explanations.

[0392] Any section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described. Brief Description of the Figures

[0393] Aspects and embodiments of the present invention will now be discussed with reference to the accompanying figures in which: Figure 1 shows photograph of emulsions prepared using the above protocol for SB- P-86, SB-P-229, SB-P-230. SB-P-238, SB-P-231 and SB-P-248. E / O denotes emulsion only with no peptide. For SB-P-238, the emulsion produced was semi- transparent. Figure 2 shows the experimental set up for the testing in Plutella xylostella. Figure 3 shows activity data of peptides at 1 X 10-4M in emulsion formulations 7 days after application against Plutella xylostella in a spray assay performed by FERA. Figure 4 shows HPLC trace of SB-P-138. Figure 5 shows LCMS traces of SB-P-138. EXAMPLES

[0394] The invention will now be demonstrated and further described by way of the following non-limiting examples. Table of Peptide Codes / Sequences / MWt.Peptide chemical structuresSynthesis procedures and schemes. Procedures

[0395] All amino acids are ofL-configuration unless otherwise stated. Reagents were purchased from CEM Corporation, Iris Biotech or Doug Discovery. Peptide-grade N-butyl pyrrolidine (Tamisolve) was purchased from CEM Corporation.

[0396] Peptides were synthesised on a CEM Liberty Blue microwave assisted peptide synthesiser.

[0397] Fmoc-protected amino acids were prepared as a 0.2 M solution in N-butyl pyrrolidine. 5 equivalents of amino acid (relative to the resin loading) were used during coupling cycles. Oxyma and diisopropyl carbodiimide (DIC) were prepared as 0.5 M (solutions in N-butyl pyrrolidine.5 equivalents of Oxyma and 5 equivalents of DIC (relative to resin loading) were used during coupling cycles. For Fmoc-deprotections, a solution of 20% pyrrolidine in N-butyl pyrrolidine was used. Coupling reactions were performed under microwave heating at 90 °C for 2 min with the exception of Fmoc-Cys(Trt)-OH, Fmoc- His(Trt)-OH and Fmoc-Arg(Pbf)-OH. Coupling of Fmoc-Cys(Trt) and Fmoc-His(Trt)-OH was performed for 10 min at 50 °C. Coupling of Fmoc-Arg(Pbf)-OH was performed for 2 successive cycles (double-coupled) for 5 min at 75 °C. Microwave-assisted Fmoc deprotections were carried out at 90 °C for 1 min.

[0398] Peptides were typically cleaved from the resin in bulk by gently rocking the resin at rt in a cleavage cocktail of TFA / TIS / H2O / DODT (94:2.5:2.5:1) for 2 h before being drained and the TFA blown off with a steady stream of N2gas. In all cases the crude peptide was triturated with cold Et2O. Et2O was removed from the resulting crude peptide pellet under a steady stream of nitrogen. The crude peptide was then redissolved in H2O / MeCN and purified by RP-HPLC.

[0399] Peptides were purified on a reverse-phase CEM Prodigy HPLC system equipped, using a Phenomenex, Luna, C18, 5 μm, 150 x 30 mm column. Gradients were performed using solvents consisting of A (H2O + 0.1% TFA) and B (MeCN + 0.1% TFA) andfractions were lyophilised on a Christ Alpha 2-4 LO plus freeze dryer.

[0400] Pure peptides were analysed on an Agilent 1260 Infinity II reverse-phase HPLC (RP-HPLC) system using a Phenomenex, Luna, 5 µm, peptide XB-C18, 150 x 4.6 mm column at a flow rate of 1 mL / min. RP-HPLC gradients were run using a solvent system consisting of solution A (100% H2O + 0.1% TFA) and B (100% MeCN + 0.1% TFA). Typically, a gradient from 5% to 95% solution B over 35 min (incorporating a 2 min hold at 5% solution B and a 5 min wash at 95% solution B at the start and end of the gradient respectively) was used for characterisation. In some cases specialised gradients were used and this is indicated where appropriate. Analytical RP-HPLC data is reported as column retention time (tR) in minutes (min). Analytical columns were maintained at 30 °C.

[0401] LC-MS analysis was performed on an Agilent 6130 quadropole mass spectrometer of m / z range 50-2000 Da with an ESI source coupled to an Agilent 1260 Infinity II RP-HPLC. Analyses were performed on an Advanced Materials Technology HALO C18, 160 Å 150 x 4.6 mm column. Gradients were run using a solvent system consisting of solution A (100% H2O + 0.1% formic acid) and B (100% MeCN + 0.1% formic acid). Typically, a gradient from 5% to 95% solution B over 10 min (incorporating a 2 min hold at 5% solution B and a 2 min wash at 95% solution B at the start and end of the gradient respectively) was used for characterisation. In some cases, specialised gradients were used and this is indicated where appropriate. LC-MS column oven temperature was maintained at 30 °C. SB-P-86SB-P-229SB-P-229 (SEQ ID NO: 27)Chemical Formula: 0471-^5^ ! O14Exact Mass: 1007.47Molecular Weight: 1008.10SB-P-230SB-P-230Chemical Formula: C54H70N12O-|4 Exact Mass: 1110.51Molecular Weight: 1111.22SB-P-248SB-P-248Chemical Formula: C52H67NnO 14Exact Mass: 1069.49Molecular Weight: 1070.17SB-P-138(SEQ ID NO: 51)(SEQ ID NO: 54)

[0402] A specific synthesis route for SB-P-138 is shown above. Synthesis was carried out on the CEM Liberty Blue using Rink Amide ProTide resin (f = 0.18 mmol / g). Fmoc-deprotection reactions were carried out for 1 min at 90 °C. 2 min coupling cycles performed at 90 °C using 5 eq Fmoc-AA (relative to resin loading) and 5 eq DIC / Oxyma Pure (relative to resin loading) in TamiSolve were used for all amino acids, with the exception of Fmoc-Arg(Pbf)-OH. Arg coupling cycles were performed using two successive 5 min coupling steps at 75 °C. Extended 4 min coupling methods were used for Leu2, Thr5 and Nal8.

[0403] Post-synthesis, simultaneous resin-cleavage and sidechain deprotection was performed in a cocktail of 94: 2.5: 2.5: 1 (v / v) TFA: TIS: H2O: DODT for 2 h at roomtemperature. Following trituration in ice-cold Et2O and lyophiliyation, the crude peptides were purified via RP-HPLC and purity was then assessed by HPLC and LCMS.

[0404] Purification was performed on a Prodigy system; 20-40% B 20 mL / min 254 nm 30 min tR = 10.7; dissolved in 20% MeCN. Characterisation was performed as follows. Analytical HPLC: standard 35 min gradient tR = 15.5, purity = 98%. LCMS: standard 10 min gradient [M+H]+ = 1090.4, MW = 1089.5. Yield = 20 mg, 18%. Characterisation of SB-P-138 is shown in Figure 4 and Figure 5. Peptide Formulation. Emulsification Protocol Lyophilised peptide powder (s, 1x10-4M final concentration) and sodium chloride granules (s, 1x10-2M final concentration) were dispersed in methyl oleate (l, final concentration 3% v / v) by sonication. Silwet 408 (l, final concentration 0.05% v / v) was added. The dispersion was diluted with MilliQ water. The mixture was then vortex mixed at 2840 rpm for 1 min and sonicated for 15 min. This 1 min vortex mix and 15 min sonication cycle was then repeated once. This procedure afforded an opaque, white emulsion. Emulsions are shown in Figure 1. Fura-2 based Calcium assay The Fura-2 based Calcium assay relies upon the specific properties of the Fura-2 dye as a calcium binding, ratiometric fluorescent dye that is cell permeable. During the assay, adherent cells expressing known neuropeptide GPCR targets will be challenged with neuropeptides, resulting in activation of the GPCR which causes a cascade of molecular events eventually leading to a sharp rise in intracellular calcium levels. With Fura-2 present within the cells, this calcium spike is translated into a change in fluorescence at both 340nm and 380nm using 495nm as the excitation wavelength. When Fura-2 is bound to calcium and excited using 495nm light, it produces 340nm light, while if it is not bound to calcium it produces 380nm light in the same conditions. This change is due to the specific structural changes in Fura-2 with calcium bound. This results in the amount of 380nm light decreasing to the same extent the 340nm light is increasing, during a downstream calcium signalling event within living cells while being exposed to 495nm light with Fura-2 present. To prepare the cell plate, the media should first be removed from the plate using an aspirator. The Fura-2 aliquots should then be added to the 12 mL of media in a pipetting boat. Using a multichannel pipette, 100 µL of this mixture is dispensed into each well of the plate. The plate should then be incubated in a 37 °C incubator with 5% CO2for 45 minutes. For preparing the compound plate, the dilutions for the peptides are set up for transfer to the cell plate. First, 150 µL of the vehicle is added to each well in the bottom row of the plate.Then, 150 µL of each peptide dilution is added to each row of the plate, ascending in concentration from bottom to top. The least potent dilutions, such as 2x10⁻¹¹, are added just above the vehicle row, while the most potent dilutions, like 2x10⁻⁵, are added to the top row. Each peptide is added to only three wells in each row; for example, columns 1-3 will receive the first peptide, columns 4-6 the second, columns 7-9 the third, and columns 10-12 the fourth. After the 45-minute incubation, the cell plate is removed from the incubator, and the Fura-2 media is aspirated. Each well is washed with 100 µL of HBSS using a multichannel pipette, and the media is aspirated again. This wash step is repeated once. After the two washes, 100 µL of HBSS is added to each well, and the buffer is left in the wells. The plate is then stored in a 37 °C incubator along with the compound plate for an additional 15 minutes. Once the final 15-minute incubation period is complete, the plate is ready for analysis. The plate reading is then started. Once the assay has run its course, the results can be visualized and data can be pasted into Prism software for comprehensive analysis. EC50 values and comments on bifunctionality.The above data demonstrate that, while the native peptide SB-P-86 displays in vitro receptor activation only of the AKHR for S frugiperda (Sf), each of the analogues thereof display varying degrees of in vitro activation of both the S frugiperda AKHR and LKR, indicating that they may be able to bind to both receptors in vivo, affording the designs potential dual-target bifunctionality. The LogEC50 value is shown as a negative value due to the mathematical nature of log; a LogEC50 value of -9.4 corresponds to 1 x 10-9.4M concentration, which can be further changed to 0.4 nM concentration. This LogEC50 value marks the concentration that produces half the maximal effect of the peptide against the specified receptor target (AKHR and LKR). Testing in Plutella xylostella - FERA results. Test insects: Larvae (2nd / 3rdinstar) were sourced from a laboratory culture of P. xylostella. The culture was maintained in a controlled environment (CE) room with conditions of 25oC and 16:8lighting regime on Chinese cabbage plants. Potted Chinese cabbage plants (3-4 leaf stage) were used in the bioassays. Experimental conditions: A CE room set at 20 °C and 65% r.h. with a 16 hour light: 8 hours dark lighting regime, was used. Methods: Four cabbage plants per treatment were sprayed from above using a laboratory spray chamber at a rate of 200L / Ha. The plants were allowed to air dry and twenty 2nd / 3rd instar larvae were added to each plant which were then covered with a ventilated bag and secured with an elastic band (Figure 2). The plants were placed in plastic containers and watered from below. The plants were put into the experimental conditions. Mortality counts were performed at seven days post treatment. Results and Discussion In all replicates less than the original twenty larvae were recovered. This may have been due to cannibalism (although the larvae did not completely decimate the cabbage plants) or reduced numbers of larvae actually introduced (due to handling) or failure to find all the larvae (if present in the soil). However, this was consistent in all replicates and has been observed in previous experiments. Results are shown in Figure 3. References

[0405] A number of publications are cited in order to more fully describe and disclose the invention and the state of the art to which the invention pertains. Full citations for these references are provided below. The entirety of each of these references is incorporated herein by reference. o Koyama T, Terhzaz S, Naseem MT, Nagy S, Rewitz K, Dow JAT, Davies SA, Halberg KV. A nutrient-responsive hormonal circuit mediates an inter-tissue program regulating metabolic homeostasis in adult Drosophila. Nat Commun. 2021 o Gäde G, Auerswald LGen Comp Endocrinol. 2003 Jun 1;132(1):10-20. doi: 10.1016 / s0016-6480(03)00159-x o Yeoh JGC, Pandit AA, Zandawala M, Nässel DR, Davies SA, Dow JAT. DINeR: Database for Insect Neuropeptide Research. Insect Biochem Mol Biol.2017o 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, Halyomorpha halys (Hemiptera: Pentatomidae). Front Physiol.2020 o Audsley N and Down RE, G protein coupled receptors as targets for next generation pesticides. Insect Biochem Molec 67: 27-37 (2015). o Halberg KA, Terhzaz S, Cabrero P, Davies SA and Dow JAT, Tracing the evolutionary origins of insect renal function. Nat Commun 6 (2015). o 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). o 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). o Predel R, Wegener C, Biology of the CAPA peptides in insects. Cell Mol Life Sci 63: 2477-2490 (2006). o Lamango NS, Nachman RJ, Hayes TK, Strey A and Isaac RE, Hydrolysis of insect neuropeptides by an angiotensin converting enzyme from the housefly, M. domestica. Peptides 18: 47-52 (1997). o 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 functional homology to human neuromedinU receptor. PLoS One 7(1): e29897 (2012). o IRAC susceptibility test method 019 (https: / / irac-online.org / methods / aphids- adultnymphs / ). o For standard molecular biology techniques, see Sambrook, J., Russel, D.W. Molecular Cloning, A Laboratory Manual. 3 ed. 2001, Cold Spring Harbor, New York: Cold Spring Harbor Laboratory Press

Claims

-CLAIMS- 1. A bifunctional peptide capable of binding to both AKH and kinin receptors; wherein the peptide has the formula (I) below: R1-X-Y-Z-R2(I) wherein: R1is hydrogen (which may be designated "H-" or "Hy-"), C1-4alkyl (e.g. methyl, ethyl, propyl, butyl), formyl, or pyroglutamate; X is absent or is selected from Q#or E#; Y is a peptide moiety of the formula: Y1- Y2- F#-Y4wherein: Y1is L#, I#or V#; Y2is N#, T#or S#; Y4is absent or is selected from S#or T#; Z is a peptide moiety of the formula: Z1-Z2-Z3-W#-Z5-Z6wherein: Z1is absent or is selected from F#, T#or Y#; Z2is selected from S#, Y#, K#, N#or H#; Z3is selected from S#, A#, P#, V#or T#; Z5is selected from G#, A#; Z6is absent or is G#; wherein “ ” indicates that the residue is independently the listed unmodified amino acid, a modified amino acid or a non-natural amino acid analogue; and R2is NH2, NR2aH or NR2aR2b; wherein each of R2aand R2bif present are independently C1-6-alkyl (e.g. methyl, ethyl, propyl, butyl, pentyl or hexyl); wherein if X is Q#or E#, then R1is not pyroglutamate.

2. The bifunctional peptide according to claim 1, wherein at least one of the following provisos applies; i) the peptide is not [pyr]LTFTSSWGG-NH2 (SEQ ID NO: 33); or ii) if Y4is T, then Z6is absent; or iii) if Y4is T, and Z1is absent, then Z6is absent.

3. The bifunctional peptide according to claim 1 or claim 2, wherein the peptides demonstrate a LogEC50of -5.0 or less against a kinin receptor; and a LogEC50of -5.0 or less against an AKH receptor.

4. The bifunctional peptide according to any one of the preceding claims, wherein: Y is a peptide moiety of the formula (Y1): L#-T#-F#-Y4(Y1) wherein Y4is absent or is T#; whereinindicates that the residue is independently the listed unmodified amino acid, a modified amino acid or a non-natural amino acid analogue; optionally, wherein Y is a peptide moiety of the formula (Y1a) or (Y1b): L#-T#-F#-T#(Y1a) (SEQ ID NO : 1) L#-T#-F#(Y1b) wherein “ ” indicates that the residue is independently the listed unmodified amino acid, a modified amino acid or a non-natural amino acid analogue; optionally wherein Y comprises no more than one modified amino acid or a non-natural amino acid analogue.

5. The bifunctional peptide according to any one of the preceding claims, wherein Y has a formula selected from: L-T-F-T (SEQ ID NO: 2); or L-T-F.

6. The bifunctional peptide according to any one of claims 1 to 3, wherein Z is a peptide moiety of the formula (Z1):Z1-S#-S#-W#-G#-Z6(Z1) (SEQ ID NO: 3) Z1is absent or is selected from F#or Y#; and Z6is absent or is G#.

7. The bifunctional peptide according to any one of the preceding claims, wherein Z has a formula selected from (Z1a), (Z1b), (Z1c), (Z1d) or (Z1e): S#-S#-W#-G#-G#(Z1a) (SEQ ID NO: 4) S#-S#-W#-G#(Z1b) (SEQ ID NO: 5) F#-S#-S#-W#-G#-G#(Z1c) (SEQ ID NO: 6) F#-S#-S#-W#-G#(Z1d) (SEQ ID NO: 7) Y#-S#-S#-W#-G#(Z1e) (SEQ ID NO: 8) wherein “ ” indicates that the residue is independently the listed unmodified amino acid, a modified amino acid or a non-natural amino acid analogue; optionally wherein Z comprises no more than three modified amino acid or a non-natural amino acid analogue.

8. The bifunctional peptide according to any one of the preceding claims, wherein Z has a formula selected from (Z2a), (Z2b), (Z2c), (Z2d) or (Z2e): S#-S#-W#-G-G (Z2a) (SEQ ID NO: 9) S#-S#-W#-G (Z2b) (SEQ ID NO: 10) F#-S#-W#-G-G (Z2c) (SEQ ID NO: 11) F#-S#-S#-W#-G (Z2d) (SEQ ID NO: 12) Y#-S#-S#-W#-G (Z2e) (SEQ ID NO: 13) wherein “ ” indicates that the residue is independently the listed unmodified amino acid, a modified amino acid or a non-natural amino acid analogue; optionally wherein Z has a formula selected from (Z3a), (Z3b), (Z3c), (Z3d) or (Z3e): S#-S-W-G-G (Z3a) (SEQ ID NO: 14) S#-S-W-G (Z3b) (SEQ ID NO: 15) F#-S-W-G-G (Z3c) (SEQ ID NO: 16) F#-S-S-W-G (Z3d) (SEQ ID NO: 17)Y#-S-S-W-G (Z3e) (SEQ ID NO: 18) wherein “ ” indicates that the residue is independently the listed unmodified amino acid, a modified amino acid or a non-natural amino acid analogue.

9. The bifunctional peptide according to any one of the preceding claims, wherein Z has a formula selected from: [n-me-S]-S-[Nal]-G-G (SEQ ID NO: 19); [n-me-S]-[s]-[Nal]-G-G (SEQ ID NO: 52);S-S-W-G-G (SEQ ID NO: 20); S-S-W-G (SEQ ID NO: 21); F-S-S-W-G-G (SEQ ID NO: 22); F-S-S-W-G (SEQ ID NO: 23); Y-S-S-W-G (SEQ ID NO: 24); [Thi]-S-S-W-G (SEQ ID NO: 25).

10. The bifunctional peptide according to any one of the preceding claims, wherein if at least one of the residues in peptides X, Y and / or Z is a modified amino acid or non-natural amino acid analogue, then the modified amino acid or non-natural amino acid analogue is selected from: i. an N-methylated amino acid; i. a non-proteinogenic amino acid, e.g. hydroxyproline (Hyp: L- hydroxyproline or (2S,4R)-4-Hydroxyproline), Octahydroindole-2- carboxylic acid (Oic), sarcosine (Sar), norleucine (Nle), α- aminoisobutyric acid (Aib), thienyl alanine (Thi) or thiazolidine-4- carboxylic acid (Thz), phenylglycine (Phg), gamma aminobutyric acid (gaba) or naphthylalanine (Nal); ii. a D-amino acid iii. a beta-amino acid iv. a peptoid amino acid analogue; v. a sugar modified amino acid; or vi. a biotin modified amino acid;or the side chains of two amino acid residues may be joined together to form a cyclic structure (e.g. intramolecular amide formation via condensation reaction between the side chains of arginine or lysine, with the side chain of aspartic acid or glutamic acid); optionally wherein if at least one of the residues in peptides X, Y and / or Z is a modified amino acid or non-natural amino acid analogue, then the modified amino acid or non-natural amino acid analogue is selected from: ii. an N-methylated amino acid; iii. a peptoid amino acid analogue; iv. a non-proteinogenic amino acid, selected from hydroxyproline (Hyp: L- hydroxyproline or (2S,4R)-4-Hydroxyproline), Octahydroindole-2- carboxylic acid (Oic), sarcosine (Sar), norleucine (Nle), α- aminoisobutyric acid (Aib), thienyl alanine (Thi), thiazolidine-4- carboxylic acid (Thz) or naphthylalanine (Nal); v. a D-amino acid.

11. The bifunctional peptide according to any one of the preceding claims, wherein if at least one of the residues in peptides X, Y and / or Z is a modified amino acid or non-natural amino acid analogue, then the modified amino acid or non-natural amino acid analogue is selected from: i. an N-methylated amino acid; ii. thienyl alanine (Thi); iii. thiazolidine-4-carboxylic acid (Thz) iv. naphthylalanine (Nal); or v. a D-amino acid.

12. An bifunctional peptide according to any one of the preceding claims, wherein Y-Z taken together form a peptide of the formula: LTFT[n-me-S]S[Nal]GG (SEQ ID NO: 44); LTFT[n-me-S][s][Nal]GG (SEQ ID NO: 53); LTFTSSWG (SEQ ID NO: 45); LTFFSSWGG (SEQ ID NO: 46);LTFFSSWG (SEQ ID NO: 47); LTFTFSSWG (SEQ ID NO: 48); LTFYSSWG (SEQ ID NO: 49); or LTF[Thi]SSWG (SEQ ID NO: 50); optionally wherein Y-Z taken together form a peptide of the formula: LTFTSSWG (SEQ ID NO: 45); LTFFSSWGG (SEQ ID NO: 46); LTFFSSWG (SEQ ID NO: 47); LTFTFSSWG (SEQ ID NO: 48); or LTFYSSWG (SEQ ID NO: 49).

13. An bifunctional peptide according to any one of the preceding claims, wherein R1 is selected from R1is selected from hydrogen, C1-2alkyl or pyroglutamate; optionally wherein R1 is selected from hydrogen or pyroglutamate; further optionally wherein R1 is pyroglutamate.

14. An bifunctional peptide according to any one of the preceding claims, wherein R2 is selected from R2is NH2, NR2aH or NR2aR2b; wherein each of R2aand R2bare independently selected from C1-2-alkyl ; optionally wherein R2 is selected from R2is NH2 or NMe2; further optionally wherein R2 is NH2.

15. An bifunctional peptide according to claim 1, or a salt or solvate thereof, selected from: [pyr]-LTFT[n-me-S][s][Nal]GG-NH2 (SEQ ID NO: 54); [pyr]LTFTSSWG-NH2 (SEQ ID NO: 27); [pyr]LTFFSSWGG-NH2 (SEQ ID NO: 28); [pyr]LTFFSSWG-NH2 (SEQ ID NO: 29); [pyr]LTFTFSSWG-NH2 (SEQ ID NO: 30); [pyr]LTFYSSWG-NH2 (SEQ ID NO: 31);[pyr]LTF[Thi]SSWG-NH2 (SEQ ID NO: 32); or [pyr]-LTFT[n-me-S]S[Nal]GG-NH2 (SEQ ID NO: 26).

16. A composition, e.g. an insect control composition or plant protection composition, comprising a bifunctional peptide according to any one of claims 1 to 15 in admixture with one or more solvents, carriers, diluents, adjuvants, preservatives, dispersants, emulsifying agents, or synergists; optionally wherein the composition is an aqueous composition.

17. A composition according to claim 16, which further comprises one or more of a kinin peptide, an AKH peptide, a DH31 peptide, a DH44 peptide, a pyrokinin peptide or a CAPA peptide (e.g. a CAPA-1, CAPA-2 or CAPA-3 analogue).

18. Use of a bifunctional peptide according to any one of claims 1 to 15, or a composition according to claim 16 or 17, as either: i) an insect control agent; or ii) as a plant protection agent for protecting a plant or part thereof against insects.

19. The use according to claim 18, wherein the insects are lepidopteran insects, preferably wherein the lepidopteran insects are selected from: Plutella xylostella or Spodoptera frugiperda.

20. A method of increasing insect mortality, the method comprising contacting an insect or insect population with a bifunctional peptide according to any one of claims 1 to 15, or a composition according to claim 16 or 17.

21. A method of inhibiting or preventing infestation of a plant by insects, the method comprising contacting the plant or a part thereof, or a site on which the plant is growing or is intended to be grown, with a bifunctional peptide according to any one of claims 1 to 15, or a composition according to claim 16 or 17;optionally wherein the bifunctional peptide or composition is contacted with the plant or part thereof, or a site on which the plant is growing or is intended to be grown, while the plant or part is free or substantially free of insects.

22. A method of reducing or treating an insect infestation of a plant, or of reducing insect load on a plant, the method comprising contacting the plant or a part thereof, or a site on which the plant is growing, with a bifunctional peptide according to any one of claims 1 to 15, or a composition according to claim 16 or 17.

23. The method according to any one of claims 16 to 18, wherein one or more of the following applies: a) the site on which the plant is growing or intended to be grown may comprise an agricultural site suitable for growing plants, preferably the site comprises a field; b) contacting the insect or insect population, plant or part thereof, or site, comprises watering feeding, spraying, atomizing, foaming, fogging, culturing in hydroculture, culturing in hydroponics, coating, submerging, and / or encrusting the insect or insect population, plant or part thereof, or site with the bifunctional peptide or composition; and / or c) the insect or insect population, plant or part thereof, or site, is contacted with an effective concentration of the bifunctional peptide, preferably a concentration of between 10-3to 10-9M.

24. The method according to any of claims 16 to 19, wherein the insects are lepidopteran insects, preferably wherein the lepidopteran insects are selected from: Plutella xylostella or Spodoptera frugiperda.

25. A method of producing a bifunctional insect neuropeptide, said method comprising the steps of: a. selecting a naturally occurring AKH peptide; and b. modifying the C-terminal region of the naturally occurring AKH peptide so that it comprises a kinin motif.

26. The method of claim 25, wherein the kinin motif has a formula Z-R2, wherein: Z is a peptide moiety of the formula:Z1-Z2-Z3-W#-Z5-Z6wherein: Z1is absent or is selected from F#, T#or Y#; Z2is selected from S#, Y#, K#, N#or H#; Z3is selected from S#, A#, P#, V#or T#; Z5is selected from G#, A#; Z6is absent or is G#; whereinindicates that the residue is independently the listed unmodified amino acid, a modified amino acid or a non-natural amino acid analogue; and R2is NH2, NR2aH or NR2aR2b; wherein each of R2aand R2bif present are independently C1-6-alkyl (e.g. methyl, ethyl, propyl, butyl, pentyl or hexyl).

27. The method of claim 25 or 26, wherein the bifunctional insect neuropeptide has a formula (I) as defined in claim 1.

28. The method of any of claims 25 to 27 wherein the C-terminal region of the naturally occurring AKH peptide comprises the C-terminal 4 to 6 amino acids of the AKH peptide.

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