Angiotensin-converting enzyme (ACE) inhibiting peptides.

Abstract

Provided are with angiotensin-converting enzyme (ACE) inhibitory activity, and compositions comprising one or more of the peptides. The peptides have a use to treat or prevent hypertension. The peptides find a further use providing muscle health benefits and improving sexual function.

Description

Title of the inventionAngiotensin-converting enzyme (ACE) inhibiting peptides.Field of the InventionThe current invention relates to peptides and compositions comprising said peptides. The peptides of the invention have angiotensin-converting enzyme (ACE) inhibitory activity. The current invention also relates to the use of peptides and compositions of the invention. The current invention further relates to methods using the peptides and compositions of the invention.Background to the InventionBlood pressure is the force applied to blood vessels as blood travels in circulation. Hypertension, or high blood pressure, is a condition that occurs when the force of blood against blood vessels is consistently too high, thus putting a strain on both blood vessels and the heart.A recent World Health Organisation (WHO) study found 1.13 billion people globally now have high blood pressure, meaning that more than 1 in 5 adults are currently affected by this condition. Hypertension is difficult to diagnose as most people present no identifiable symptoms. Consequently, it is known as a “silent killer”, accounting for 7.5 million deaths worldwide each year (WHO, 2014).Stressful and competitive lifestyles and food habits have compounded the problems of hypertension. Rising hypertension can lead to a range of conditions, such as heart failure and myocardial infarction (Ml). ACE inhibitors have been used in therapy for cardiovascular and renal disease. ACE inhibitors have proven effective in the treatment of hypertension (Hanif, K., et al., Reinventing the ACE inhibitors: some old and new implications of ACE inhibition. Hypertens Res 33, 11-21 (2010)). ACE has a pivotal role in the balance between vasodilatory and natriuretic properties of bradykinin, and vasoconstrictive and salt-retentive properties of Angiotensin II (Ang II). An increase in ACE activity disturbs this delicate balance and promotes vasoconstrictive and salt-retentive Ang II and decreases vasodilatory and natriuretic bradykinin. This narrowing of the blood vessels, or vasoconstriction, and decrease in bradykinin, causes high blood pressure. ACE inhibitors restore this balance by preventing or decreasing formation of Ang II and the degradation of bradykinin.Nitric Oxide (NO) is a gas molecule that is produced by nearly every type of cell in the body in most body tissues, including blood vessels. It is a chemical messenger and one of its functions to promote dilation of blood vessels. It works by relaxing the inner wall of the blood vessel, particularly the large arteries and veins. This enables blood to flow smoothly and maintains ahealthy level of blood pressure. NO has been used as a therapeutic option for patients with pulmonary hypertension since 1999.NO also causes vasodilation in the sexual organs. Medications, such as Viagra (sildenafil) and Cialis (tadalafil), work by increasing nitric oxide levels in order to stimulate blood flow into sexual organs.Vasodilation has a number of benefits for muscle health. Increased blood flow to muscles provides them with more oxygen and nutrients, which strengthens the muscle and prevents or reduces degeneration.For athletes or anyone who exercises, vasodilation can aid recover after performance. It increases relaxation, reduces swelling and pain and increases blood flow, all which help the muscle recover fast after performance. Sports massage and NO producing supplements are commonly used by athletes. This recovery benefit is also useful in recovery after injury or surgery. Increased blood flow helps to carry away waste or excess fluid from the injury site while providing it with more oxygen and nutrients for muscle repair. Muscle tightness and pain are also reduced.Vasodilation also helps to prepare for better performance in exercise or competition. The increased blood flow allows more oxygen and nutrients to the muscles which helps performance. Increased blood flow also causes the muscles to relax which decreases injury risk.The current invention serves to solve one or more problems of the prior art by providing a product, such as a food product, that promotes vasodilation by acting as an ACE inhibitor and / or modulating downstream mediators of vasodilation, such as NO.Summary of the InventionThe current inventors have found peptides that promote vasodilation. The peptides of the invention act by inhibiting ACE (Figure 1 and 2) and / or by modulating mediators of vasodilation, such as NO. Thus, the peptides of the invention have a use to treat or prevent hypertension.Vasodilation also has a number of benefits for muscle health and sexual function. Therefore, the peptides find a further use in providing muscle health benefits and improving sexual function.The inventors also found that the peptides have anti-inflammatory properties and can affect ATP production rate. Thus the peptides have a still further use in treating and preventing inflammation and in increasing energy or reducing fatigue.An aspect of the current invention provides a peptide, typically up to 50 amino acids in length, comprising (or consisting of) an amino acid sequence selected from SEQUENCE ID NO. 1 to SEQUENCE ID NO. 30, or a variant of the amino acid sequence (herein after referred to as “peptide of the invention”).The amino acid sequences of SEQUENCE ID NO. 1 to 30 are as follows:In an embodiment, the peptide of the invention is bioactive.The peptides of the invention have ACE inhibitory activity. This activity promotes vasodilation.In an embodiment, the peptides of the invention have NO modulating activity.In an embodiment, the peptides of the invention have anti-inflammatory activity.In an embodiment, the peptides of the invention affect ATP production rates.In an embodiment, the peptide of the invention is a modified peptide. In an embodiment, the peptide is modified to increase its lipophilicity. In an embodiment, the peptide is modified to increase its half-life. In an embodiment, an N-terminal or C-terminal amino acid of the peptide is modified. In an embodiment, the peptide is modified with a protecting group. In one embodiment, the N-terminal or C-terminal amino acid of the peptide is modified with a protecting group.An aspect of the invention provides a conjugate comprising one or more peptides of the invention conjugated or linked, or fused, to a binding partner (herein referred to as “the conjugate of the invention”). In an embodiment, the peptide of the invention is modified with a reactive group or similar, configured to allow conjugation to the binding partner.An aspect of the invention provides a composition comprising one or more peptides of the invention (herein referred to as “the composition of the invention”). The composition of the invention may comprise at least 2 peptides of the invention, preferably 3 or more peptides of the invention, preferably 4 or more peptides of the invention, preferably 5 or more peptides of the invention.In an embodiment, the composition of the invention is a powder. The powder is a food grade powder, i.e. , suitable for addition to food or feed compositions.In an embodiment, the powder comprises about 0.0001 to about 1.0%, about 0.0001 to about 0.2%, about 0.001 to about 0.1%, or about 0.01 to about 0.1%, of the one or more peptides of the invention (w / w).In an embodiment the composition is edible (comestible). In one embodiment, the composition is a food or beverage. It is one suitable for mammalian consumption, preferably for human consumption.In an embodiment, the composition is nutritional or dietary supplement.In an embodiment, the composition is a pharmaceutical composition, optionally comprising at least one pharmaceutically acceptable excipient.Preferably, the composition is man-made.An aspect of the invention provides a peptide of the invention or a composition of the invention for use in a method of treating or preventing hypertension in a subject.An aspect of the invention provides a peptide of the invention or a composition of the invention for use in a method of reducing blood pressure in a subject.An aspect of the invention provides a peptide of the invention or a composition of the invention for use in a method for causing or promoting vasodilation in a subject.In an embodiment, the subject is one with high blood pressure and / or a heart condition. Heat conditions include peripheral vascular disease, autoimmune conditions effecting blood flow and sarcopenia.An aspect of the invention provides a peptide of the invention or a composition of the invention for use in a method to prevent or treat early hypertension in a subject. The subject may be one at risk of developing hypertension.An aspect of the invention provides a peptide of the invention or a composition of the invention for use in improving sexual function in a subject.An aspect of the invention provides a peptide of the invention or a composition of the invention for use in restoring declined sexual function in a subject.An aspect of the invention provides a peptide of the invention or a composition of the invention for use in increasing libido in a subject.The subject may be one with a sexual function disorder, such as erectile dysfunction. The subject may be one with normal sexual function.There are many reasons why muscle health is crucial. Firstly, muscle loss causes immobility and, with an ageing population on the rise, this is becoming a huge problem. Secondly, active individuals want to maintain their muscle mass, remain athletic, competitive and healthy.An aspect of the invention provides a peptide of the invention or a composition of the invention for use in improving muscle status in a subject.An aspect of the invention provides a peptide of the invention or a composition of the invention for use in promoting recovery of muscle in a subject. This may be after exercise or injury, including surgery.An aspect of the invention provides a peptide of the invention or a composition of the invention for use in maintaining or improving muscle health in a subject.An aspect of the invention provides a peptide of the invention or a composition of the invention for use in enhancing physical performance in a subject, e.g. during exercise.As aspect of the invention provides a peptide of the invention or a composition of the invention for use in reducing inflammation in a subject.As aspect of the invention provides a peptide of the invention or a composition of the invention for use in preventing or treating an inflammatory disorder in a subject.As aspect of the invention provides a peptide of the invention or a composition of the invention for use in increasing energy in a subject.As aspect of the invention provides a peptide of the invention or a composition of the invention for use in reducing fatigue in a subject.As aspect of the invention provides a peptide of the invention or a composition of the invention for use in treating or preventing post-infection fatigue in a subject, e.g. a viral or bacterial infection.An aspect of the invention provides a method to improve sexual function in a subject, comprising administering a peptide or a composition of the invention to the subject. In an embodiment, the method is non-therapeutic.An aspect of the invention provides a method to restore declined sexual function in a subject, comprising administering a peptide or a composition of the invention to the subject. In an embodiment, the method is non-therapeutic.An aspect of the invention provides a method to increase libido in a subject, comprising administering a peptide or a composition of the invention to the subject. In an embodiment, the method is non-therapeutic.An aspect of the invention provides a method to improve muscle status in a subject, comprising administering a peptide or a composition of the invention to the subject. The method may be non-therapeutic.An aspect of the invention provides a method to promote muscle recovery in a subject, comprising administering a peptide or a composition of the invention to the subject. The method may be non-therapeutic.An aspect of the invention provides a method to maintain or improve muscle health in a subject, comprising administering a peptide or a composition of the invention to the subject. In an embodiment, the method is non-therapeutic.An aspect of the invention provides a method to enhance physical performance in a subject, comprising administering a peptide or a composition of the invention to the subject. In an embodiment, the method is non-therapeutic.An aspect of the invention provides a method to reduce inflammation in a subject, comprising administering a peptide or a composition of the invention to the subject. In an embodiment, the method is non-therapeutic.An aspect of the invention provides a method to prevent or treat an inflammatory disorder in a subject, comprising administering a peptide or a composition of the invention to the subject.An aspect of the invention provides a method to increase energy in a subject, comprising administering a peptide or a composition of the invention to the subject. The subject may be one recovering from an illness, or an injury. The subject may be an otherwise healthy individual. In an embodiment, method is used to increase energy during exercise. In an embodiment, the method is non-therapeutic.An aspect of the invention provides a method to reduce fatigue in a subject, comprising administering a peptide or a composition of the invention to the subject. In an embodiment, the method is non-therapeutic.Use of the peptide of the invention or the composition of the invention in the above methods is also provided. In an aspect, the invention provides a nucleic acid sequence encoding one or more peptides of the invention.It is to be understood that additional ingredients listed may provide more than one benefit. The classification given herein is for clarity and convenience only and not intended to limit the additional ingredient to that particular application or category listed.In an aspect, the invention provides an expression vector comprising DNA encoding one or more peptides of the invention, in which the vector is configured for heterologous expression of the one or more peptide of the invention, in a host cell (hereafter “expression vector of the invention”).In an aspect, the invention provides a host cell, especially a bacterium or mammalian producer cell or yeast, engineered to heterologously express one or more peptides of the invention (hereafter “transformed cell of the invention”). In one embodiment, the transformed host cell comprises an expression vector on the invention.The invention also provides a method of producing one or more peptides of the invention , comprising the steps of providing a transformed cell of the invention, culturing the transformed host cell to effect heterologous expression of recombinant peptide of the invention by the host cell, and recovering the recombinant peptide of the invention.The invention also provides a method of engineering a cell for heterologous expression of one or more peptides of the invention, comprising the steps of transforming the cell with an expression vector of the invention, whereby the transformed cell is capable of heterologous expression of the one or more peptides of the invention.DefinitionsAll publications, patents, patent applications and other references mentioned herein are hereby incorporated by reference in their entireties for all purposes as if each individual publication, patent or patent application were specifically and individually indicated to be incorporated by reference and the content thereof recited in full.Where used herein and unless specifically indicated otherwise, the following terms are intended to have the following meanings in addition to any broader (or narrower) meanings the terms might enjoy in the art:Unless otherwise required by context, the use herein of the singular is to be read to include the plural and vice versa. The term “a” or “an” used in relation to an entity is to be read to refer to one or more of that entity. As such, the terms “a” (or “an”), “one or more,” and “at least one” are used interchangeably herein.As used herein, the term “comprise,” or variations thereof such as “comprises” or “comprising,” are to be read to indicate the inclusion of any recited integer (e.g. a feature, element, characteristic, property, method / process step or limitation) or group of integers (e.g. features, element, characteristics, properties, method / process steps or limitations) but not the exclusion of any other integer or group of integers. Thus, as used herein the term “comprising” is inclusive or open-ended and does not exclude additional, unrecited integers or method / process steps.As used herein, the term “disease” is used to define any abnormal condition that impairs physiological function and is associated with specific symptoms. The term is used broadly toencompass any disorder, illness, abnormality, pathology, sickness, condition or syndrome in which physiological function is impaired irrespective of the nature of the aetiology (or indeed whether the aetiological basis for the disease is established). It therefore encompasses conditions arising from infection, trauma, injury, surgery, radiological ablation, poisoning or nutritional deficiencies.As used herein, the term “treatment” or “treating” refers to an intervention (e.g., the administration of an agent to a subject) which cures, ameliorates or lessens the symptoms of a disease or removes (or lessens the impact of) its cause(s). In this case, the term is used synonymously with the term “therapy”. Can be manifested by a permanent or temporary improvement in the subject’s condition. In this context it includes limiting and / or reversing disease progression.As used herein the terms “prevention” or “preventing” refer to an intervention (e.g. the administration of an agent to a subject), which prevents or delays the onset or progression of a disease, or the severity of a disease, in a subject, or reduces (or eradicates) its incidence within a treated population.As used herein, an “therapeutically effective amount” as applied to a reference peptide or composition means an amount that can be administered to a subject without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio, but one that is sufficient to provide the desired effect, e.g. the treatment or prophylaxis manifested by a permanent or temporary improvement in the subject’s condition. The amount will vary from subject to subject, depending on the age and general condition of the individual, mode of administration and other factors. Thus, while it is not possible to specify an exact effective amount, those skilled in the art will be able to determine an appropriate "effective" amount in any individual case using routine experimentation and background general knowledge. A therapeutic result in this context includes eradication or lessening of symptoms, reduced pain or discomfort, prolonged survival, improved mobility and other markers of clinical improvement. A therapeutic result need not be a complete cure.The term “peptide” used herein refers to a polymer composed of up to 50 amino acid monomers typically via peptide bond linkage. The peptide may be 3 to 50 amino acids in length. The peptide may be 4 to 50 amino acids in length. The peptide may be 5 to 50 amino acids in length. The peptide may be 7 to 50 amino acids in length. The peptide may be 8, 9 or 10 to 50 amino acids in length. The peptide may be up to 20 or 30 amino acids in length. Peptides (including fragments and variants thereof) of and for use in the invention may be generated wholly or partly by chemical synthesis or by expression from nucleic acid. Forexample, the peptides of and for use in the present invention can be readily prepared according to well-established, standard liquid or, preferably, solid-phase peptide synthesis methods known in the art (see, for example, J. M. Stewart and J. D. Young, Solid Phase Peptide Synthesis, 2ndedition, Pierce Chemical Company, Rockford, Illinois (1984), in M. Bodanzsky and A. Bodanzsky, The Practice of Peptide Synthesis, Springer Verlag, New York (1984). When necessary, any of the peptides employed in the invention can be chemically modified to increase their stability. Typically, the peptide is a linear peptide.A “chemically modified peptide” or a “peptide analog” includes any functional chemical equivalent of the peptide characterized by its increased stability and / or efficacy in vivo or in vitro in respect of the practice of the invention. The term peptide analog also refers to any amino acid derivative of a peptide as described herein. A peptide analog can be produced by procedures that include, but are not limited to, modifications to side chains, incorporation of unnatural amino acids and / or their derivatives during peptide synthesis and the use of crosslinkers and other methods that impose conformational constraint on the peptides or their analogs. Examples of side chain modifications include modification of amino groups, such as by reductive alkylation by reaction with an aldehyde followed by reduction with NaBH4; amidation with methylacetimidate; acetylation with acetic anhydride; carbamylation of amino groups with cyanate; trinitrobenzylation of amino groups with 2, 4, 6, trinitrobenzene sulfonic acid (TNBS); alkylation of amino groups with succinic anhydride and tetrahydrophthalic anhydride; and pyridoxylation of lysine with pyridoxa-5'-phosphate followed by reduction with NABH4. The guanidino group of arginine residues may be modified by the formation of heterocyclic condensation products with reagents such as 2,3-butanedione, phenylglyoxal and glyoxal. The carboxyl group may be modified by carbodiimide activation via o-acylisourea formation followed by subsequent derivatization, for example, to a corresponding amide. Sulfhydryl groups may be modified by methods, such as carboxymethylation with iodoacetic acid or iodoacetamide; performic acid oxidation to cysteic acid; formation of mixed disulphides with other thiol compounds; reaction with maleimide; maleic anhydride or other substituted maleimide; formation of mercurial derivatives using 4-chloromercuribenzoate, 4- chloromercuriphenylsulfonic acid, phenylmercury chloride, 2-chloromercuric-4-nitrophenol and other mercurials; carbamylation with cyanate at alkaline pH. Tryptophan residues may be modified by, for example, oxidation with N-bromosuccinimide or alkylation of the indole ring with 2-hydroxy-5-nitrobenzyl bromide or sulphonyl halides. Tryosine residues may be altered by nitration with tetranitromethane to form a 3-nitrotyrosine derivative. Modification of the imidazole ring of a histidine residue may be accomplished by alkylation with iodoacetic acid derivatives or N-carbethoxylation with diethylpyrocarbonate. Examples of incorporating unnatural amino acids and derivatives during peptide synthesis include, but are not limited to,use of norleucine, 4-amino butyric acid, 4-amino-3-hydroxy-5-phenylpentanoic acid, 6- aminohexanoic acid, t-butylglycine, norvaline, phenylglycine, ornithine, sarcosine, 4-amino-3- hydroxy-6-methylheptanoic acid, 2-thienyl alanine and / or D-isomers of amino acids. Peptide structure modification includes the generation of retro-inverso peptides comprising the reversed sequence encoded by D-amino acids.In this specification, the term “sequence identity” should be understood to mean the amount of nucleotides which match between different sequences. For example, a nucleotide sequence that shares at least 98% sequence identity with a reference sequence is one in which any 98% of aligned nucleotides of the variant are identical to the corresponding nucleotides in the reference sequence across the entire length of the sequence. Sequence identity is the amount of characters which match exactly between two different sequences. Hereby, gaps are not counted, and the measurement is relational to the shorter of the two sequencesThe term “variant” is a peptide that is substantially identical to the peptide of the invention, as defined herein, but altered in respect of one or more amino acid residues. Preferably such alterations involve the insertion, addition, deletion and / or substitution of 6 or fewer amino acids, preferably 5 or fewer, 4 or fewer, even more preferably of 3 or fewer, most preferably of 1 or 2 amino acids only. Insertion, addition, and substitution with natural and modified amino acids is envisaged. The variant may have conservative amino acid changes, wherein the amino acid being introduced is similar structurally, chemically, or functionally to that being substituted. The term “variant” is also intended to include chemical derivatives of the protein, i.e. , where one or more residues is chemically derivatized by reaction of a functional side group. Also included are variants in which naturally occurring amino acid residues are replaced with amino acid analogues. Details of amino acid analogues are well known to those skilled in the art. The variant is one which maintains the activity of the peptide, such as sleep promoting activity. The alterations can be the same or different.In an embodiment, the variant is a “therapeutically effective variant”. The term “therapeutically effective variant” as applied to a reference peptide means peptides having an amino acid sequence that is substantially identical to the reference peptide, and which is therapeutically effective as defined herein, such as sleep promoting activity, i.e., it is a sleep promoting variant. Thus, for example, the term should be taken to include variants that are altered in respect of one or more amino acid residues as disclosed above. Generally, the variant will have at least 50%, 60%, 70% amino acid sequence identity, preferably at least 80% sequence identity, more preferably at least 90% sequence identity, and ideally at least 95%, 96%, 97%, 98% or 99% sequence identity with the parent sequence. It should be noted that any variantwill have principally the same therapeutic effect, or may have enhanced effect, when tested in in vitro or in vivo models of the disease.The term “variant” is also taken to encompass the term “fragment” and as such means a segment of a peptide of the invention. Typically, the fragment has between 3 to 10 contiguous amino acids in length. Typically, the fragment has between 4 to 8, or 5 to 6 contiguous amino acids in length. Generally, the fragment has a charge of -3 to +2 The charge of a peptide, fragment or region is determined using the method of Cameselle, J.C., Ribeiro, J.M., and Sillero, A. (1986). Derivation and use of a formula to calculate the net charge of acid-base compounds. Its application to amino acids, proteins and nucleotides. Biochem. Educ. 14, 131— 136.The term “subject” when used herein is any subject in need of treatment or prevention. It may be a mammal such as a human or animal. In an embodiment, it is a human subject.“Mammal” means a human or animal.When use herein the term “conjugate” refers to an embodiment of the invention in which the peptide is conjugated, linked or fused to a binding partner, for example one or more polyethylene glycol polymers or other compounds, such as molecular weight increasing compounds or lipophilic groups. The molecular weight increasing compound is any compound that will increase the molecular weight, typically by 10% to 90%, or 20% to 50% of the resulting conjugate and may have a molecular weight of between 200 and 20, 000, preferably between 500 and 10, 000. The molecular weight increasing compound may be PEG, any water-soluble (amphiphilic or hydrophilic) polymer moiety, homo or co-polymers of PEG, a monomethyl- subsitututed polymer of PEG (mPEG) and polyoxyethylene glycerol (POG), polyamino acids such as poly-lysine, poly-glutamic acid, poly-aspartic acid, particular those of L conformation, pharmacologically inactive proteins such as albumin, gelatin, a fatty acid, olysaccharide, a lipid amino acid and dextran. The polymer moiety may be straight chained or branched and it may have a molecular weight of 500 to 40000Da, 5000 to 10000 Da, 10000 to 5000, Da. The compound (binding partner) may be any suitable cell penetrating compound, such as tat peptide, penetratin, pep-1. The compound (binding partner) may be an antibody molecule. The compound (binding partner) may be a lipophilic moiety or a polymeric moiety. The lipophilic substituent and polymeric substituents are known in the art. The lipophilic substituent includes an acyl group, a sulphonyl group, an N atom, an O atom or an S atom which forms part of the ester, sulphonyl ester, thioester, amide or sulphonamide. The lipophilic moiety may include a hydrocarbon chain having 4 to 30 C atoms, preferably between 8 and 12 C atoms. It may be linear or branched, saturated or unsaturated. The hydrocarbon chain may be further substituted. It may be cycloalkane or heterocycloalkane. The peptide may be modified at theN-terminal, C-terminal or both. The polymer or compound (binding partner) is preferably linked to an amino, carboxyl or thio group and may be linked by N-termini or C-termini of side chains of any amino acid residue. The polymer or compound (binding partner) may be conjugated to the side chain of any suitable residue. The polymer or compound (binding partner) may be conjugated via a spacer. The spacer may be a natural or unnatural amino acid, succinic acid, lysyl, glutamyl, asparagyl, glycyl, beta-alanyl, gamma-amino butanoyl. The polymer or compound (binding partner) may be conjugated via an ester, a sulphonyl ester, a thioester, an amide, a carbamate, a urea, a sulphonamide. A person skilled in the art is aware of suitable means to prepare the described conjugate.In terms of “sequence homology”, the term should be understood to mean that a variant (or homolog) which shares a defined percent similarity or identity with a reference sequence when the percentage of aligned residues of the variant (or homolog) are either identical to, or conservative substitutions of, the corresponding residues in the reference sequence and where the variant (or homolog) shares the same function as the reference sequence.This alignment and the percent homology or sequence identity can be determined using software programs known in the art, for example, one alignment program is BLAST, using default parameters. Details of these programs can be found at the following Internet address: http: / / www.ncbi.nlm.nih.gov / blast / Blast.cgi.A variant (or homolog) that shares 70% sequence identity with a reference sequence is one in which any 70% of aligned residues of the variant (or homolog) are identical to, or conservative substitutions of, the corresponding residues in the reference sequence across the entire length of the sequence. Sequence identity is the amount of characters which match exactly between two different sequences. Hereby, gaps are not counted and the measurement is relational to the shorter of the two sequences.The term “natural” as applied to a peptide means a peptide that includes (a) a fragment of a plant protein, typically flava bean protein, or variants of flava bean protein. The peptides or fragments of the invention may be isolated from plant proteins or made synthetically.When used herein “C-terminal domain” as applied to a fragment means the first three amino acids at the c-terminus of the fragment.The term “N-terminal domain” as applied to a fragment means the last three amino acids at the n-terminus of the fragment.The term “bioactive” as applied to a peptide or fragment means having a health promoting effect when administered a mammal, for promoting vasodilation.The term “Modified peptide”: In an embodiment of the invention the peptide is a modified peptide. The term modified peptide is used interchangeably with the term derivative of the peptide. The modified peptide includes a peptide which has been substituted with one or more groups as defined herein. The modification may be any modified that provides the peptides and or the composition of the invention with an increased ability to penetrate a cell. The modification may be any modification that increases the half-life of the composition or peptides of the invention. In one embodiment, the group is a protecting group. The protecting group may be an N-terminal protecting group, a C-terminal protecting group or a side-chain protecting group. The peptide may have one or more of these protecting groups. The person skilled in the art is aware of suitable techniques to react amino acids with these protecting groups. These groups can be added by preparation methods known in the art, for example the methods as outlined in paragraphs

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[0107] of US2014120141. The groups may remain on the peptide or may be removed. The protecting group may be added during synthesis. In an embodiment of the invention the peptides may be substituted with a group selected from one or more straight chain or branched chain, long or short chain, saturated, or unsaturated, substituted with a hydroxyl, amino, amino acyl, sulfate or sulphide group or unsubstituted having from 1 to 29 carbon atoms. N-acyl derivatives include acyl groups derived from acetic acid, capric acid, lauric acid, myristic acid, octanoic acid, palmitic acid, stearic acid, behenic acid, linoleic acid, linolenic acid, lipoic acid, oleic acid, isosteric acid, elaidoic acid, 2-ethylhexaneic acid, coconut oil fatty acid, tallow fatty acid, hardened tallow fatty acid, palm kernel fatty acid, lanolin fatty acid or similar acids. These may be substituted or unsubstituted. When substituted they are preferably substituted with hydroxyl, or sulphur containing groups such as but not limited to SO3H, SH, orS-S. In an embodiment of the current invention, the peptide is R1-X- R2. R1 and / or R2 groups respectively bound to the aminoterminal (N-terminal) and carboxyl-terminal (C-terminal) of the peptide sequence. In one embodiment, the peptide is R1-X. Alternatively, the peptide is X- R2. Preferably, R1 is H, C1-4 alkyl, acetyl, benzoyl or trifluoroacetyl. X is the peptide of the invention; R2 is OH or NH2. In an embodiment, R 1 is selected from the group formed by H, a non-cyclic substituted or unsubstituted aliphatic group, substituted or unsubstituted alicyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, Tert-butyloxycarbonyl, 9- fluorenylmethyloxycarbonyl (Fmoc) and R5-CO-, wherein Rs is selected from the group formed by H, a non-cyclic substituted or unsubstituted aliphatic group, substituted or unsubstituted alicyclyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, substituted or unsubstituted heterocyclyl and substituted or unsubstituted heteroarylalkyl;R2 is selected from the group formed by -NR3R4, -OR3 and -SR3, wherein R3 and R4 are independently selected from the group formed by H, a non-cyclic substituted or unsubstitutedaliphatic group, substituted or unsubstituted alicyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted aralkyl; and with the condition that Ri and R2 are not a-amino acids. In accordance with another preferred embodiment, R2 is -NR3R4, -OR 3 or -SR 3 wherein Rs and R4 are independently selected from the group formed by H, substituted or unsubstituted C 1-C 24 alkyl, substituted or unsubstituted C2-C 24 alkenyl, Tert-butyloxycarbonyl, 9- fluorenylmethyloxycarbonyl (Fmoc), substituted or unsubstituted C2-C 24 alkynyl, substituted or unsubstituted C3-C 24 cycloalkyl, substituted or unsubstituted C 5-C 24 cycloalkenyl, substituted or unsubstituted Cs-C 24 cycloalkynyl, substituted or unsubstituted C 6-C 30 aryl, substituted or unsubstituted C7-C24 aralkyl, substituted or unsubstituted heterocyclyl ring of 3- 10 members, and substituted or unsubstituted heteroarylalkyl of 2 to 24 carbon atoms and 1 to 3 atoms other than carbon wherein the alkyl chain is of 1 to 6 carbon atoms. Optionally, R 3 and R 4 can be bound by a saturated or unsaturated carbon-carbon bond, forming a cycle with the nitrogen atom. More preferably R 2 is -NR3R4 or -OR 3, wherein R3 and R4 are independently selected from the group formed by H, substituted or unsubstituted C1-C 24 alkyl, substituted or unsubstituted C2-C24 alkenyl, substituted or unsubstituted C2-C24 alkynyl, substituted or unsubstituted C3-C10 cycloalkyl, substituted or unsubstituted Ce-C 15 aryl and substituted or unsubstituted heterocyclyl of 3-10 members, substituted or unsubstituted heteroarylalkyl with a ring of 3 to 10 members and an alkyl chain of 1 to 6 carbon atoms. More preferably R3 and R4 are selected from the group formed by H, methyl, ethyl, hexyl, dodecyl, or hexadecyl. Even more preferably R3 is H and R4 is selected from the group formed by H, methyl, ethyl, hexyl, dodecyl, or hexadecyl. In accordance with an even more preferred embodiment, R2 is selected from -OH and -NH2. In accordance with another embodiment of this invention R 1 is selected from the group formed by H, acetyl, lauroyl, myristoyl or palmitoyl, and R2 is -NR3R 4 or -ORs wherein Rsand R4are independently selected from H, methyl, ethyl, hexyl, dodecyl and hexadecyl, preferably R2 is -OH or -NH2. More preferably, R1 is acetyl or palmitoyl and R2 is -NH2. In a preferred embodiment, the acyl group is bound to the N-terminal end of at least one amino acid of the peptide. In an embodiment of the invention, the peptide is modified to comprise a side chain protecting group. The side chain protecting group may be one or more of the groups comprising benzyl or benzyl based groups, t-butyl-based groups, benzyloxy-carbonyl (Z) group, and allyloxycarbonyl (alloc) protecting group. The side chain protecting group may be derived from an achiral amino acid such as achiral glycine. The use of an achiral amino acid helps to stabilise the resultant peptide and also facilitate the facile synthesis route of the present invention. Preferably, the peptide further comprises a modified C-terminus, preferably an amidated C-terminus. The achiral residue may be alphaaminoisobutyric acid (methylalaine). It will be appreciated that the specific side chainprotecting groups used will depend on the sequence of the peptide and the type of N-terminal protecting group used.The term “man-made” as applied to comestible products should be understood to mean made by a human being and not existing in nature.The term “dietary supplement” means a product that is suitable for mammalian ingestion as a means of supplementing the mammals’ primary dietIn this specification, the term “composition” should be understood to mean something made by the hand of man, and not excludes naturally occurring compositions. Exemplary compositions include foods, beverages, nutritional supplements, personal care compositions, and pharmaceutical compositions.Pharmaceutical compositions”: A further aspect of the invention relates to a pharmaceutical composition comprising a peptide of the invention or a composition of peptides of the invention, admixed with one or more pharmaceutically acceptable excipients, including diluents and carriers. Even though the peptides and compositions of the present invention can be administered alone, they will generally be administered in admixture with a pharmaceutical excipient, particularly for human therapy. The pharmaceutical compositions may be for human or animal usage in human and veterinary medicine.In an embodiment of the invention the excipient may be a suitable diluent, carrier, binder, lubricant, suspending agent, coating agent, preservative, stabilisers, dyes, vehicle, solubilising agent, base, emollient, emulsifying agent, fragrance, humectant, and / or surfactants. In an embodiment, the excipient is one that affects the taste of the composition, e.g. a flavour.Examples of such suitable excipients for the various different forms of pharmaceutical compositions described herein may be found in the “Handbook of Pharmaceutical Excipients, 2ndEdition, (1994), Edited by A Wade and PJ Weller. In particular, formulations for topical delivery are described in Topical drug delivery formulations edited by David Osborne and Antonio Aman, Taylor & Francis, the complete contents of which are incorporated herein by reference.Acceptable carriers or diluents for therapeutic use are well known in the pharmaceutical art, and are described, for example, in Remington's Pharmaceutical Sciences, Mack Publishing Co. (A. R. Gennaro edit. 1985).Examples of suitable diluents include, but are not limited to, any diluent disclosed in disclosed in US2014120131 or US2004132667. Examples include ethanol, glycerol and water.Examples of suitable carriers include, but are not limited to, lactose, starch, glucose, methyl cellulose, magnesium stearate, mannitol, sorbitol and the like and any suitable carrier disclosed in US2014120131 or US2004132667. In some embodiments, the carrier may include, but is not limited to, a liquid, such as water, oils or surfactants, including those of petroleum, animal, plant or synthetic origin, polymer, oil, such as peanut oil, mineral oil, castor oil, soybean oil, alcohol, polysorbates, sorbitan esters, ether sulfates, sulfates, betaines, glycosides, maltosides, fatty alcohols, nonoxynols, poloxamers, polyoxyethylenes, polyethylene glycols, dextrose, glycerol, or digitonin. It will be understood that the carrier will be dermatologically acceptable. Preferred carriers contain an emulsion such as oil-in-water, water-in-oil, water-in-oil-in-water and oil-in-water-in-silicone emulsions. Emulsions may further contain an emulsifier and / or an anti-foaming agent.Examples of suitable binders include, but are not limited to, starch, gelatin, natural sugars such as glucose, anhydrous lactose, free-flow lactose, beta-lactose, corn sweeteners, natural and synthetic gums, such as acacia, tragacanth or sodium alginate, carboxymethyl cellulose and polyethylene glycol and any suitable binder disclosed in US2014120131 or US2004132667.Examples of suitable lubricants include, but are not limited to, sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, and sodium chloride and any suitable lubricant disclosed in US2014120131 or US2004132667.The choice of pharmaceutical excipient, including carriers or diluents, can be selected with regard to the intended route of administration and standard pharmaceutical practice. The pharmaceutical compositions may comprise as, or in addition to, the excipient any suitable carrier(s), diluent(s), binder(s), lubricant(s), suspending agent(s), coating agent(s), solubilising agent(s). Examples of suitable binders include starch, gelatin, natural sugars such as glucose, anhydrous lactose, free-flow lactose, beta-lactose, corn sweeteners, natural and synthetic gums, such as acacia, tragacanth or sodium alginate, carboxymethyl cellulose and polyethylene glycol. Examples of suitable lubricants include sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride and the like. Preservatives, stabilizers, dyes and even flavouring agents may be provided in the pharmaceutical composition. Examples of preservatives include sodium benzoate, sorbic acid and esters of p-hydroxybenzoic acid. Antioxidants and suspending agents may be also used.Compositions may be formulated in unit dosage form, i.e., in the form of discrete portions containing a unit dose, or a multiple or sub-unit of a unit dose.A person of ordinary skill in the art can easily determine an appropriate dose of one of the instant compositions or peptides to administer to a subject without undue experimentation.Typically, a physician will determine the actual dosage which will be most suitable for an individual patient or subject and it will depend on a variety of factors including the activity of the specific compound employed, the metabolic stability and length of action of that compound, the age, body weight, general health, sex, diet, mode and time of administration, rate of excretion, drug combination, the severity of the particular condition, and the individual undergoing therapy. The dosages disclosed herein are exemplary of the average case. There can of course be individual instances where higher or lower dosage ranges are merited, and such are within the scope of this invention. Depending upon the need, the peptide / composition may optionally be administered at a dose of from 0.001 to 250 mg / kg body weight. In an embodiment, the dose is 100mg, 500mg, 1000mg or 2000mg per day. This may be spread out throughout the day in 1 to 5 doses, 1 to 4, or 2 or 3 doses. It may be provided in one or more doses.“Feed grade” means the source is consumable and the enzymes used in the production of it are also safe to consume.As used herein, the term “expression vector of the invention” may be any suitable vector, including chromosomal, non-chromosomal, and synthetic nucleic acid vectors (a nucleic acid sequence comprising a suitable set of expression control elements) suitable for expression of a peptide of the invention in a cell. Examples of such vectors include derivatives of SV40, bacterial plasmids, phage DNA, baculovirus, yeast plasmids, vectors derived from combinations of plasmids and phage DNA, and viral nucleic acid (RNA or DNA) vectors. In one embodiment, the peptide-encoding nucleic acid molecule is comprised in a naked DNA or RNA vector, including, for example, a linear expression element (as described in, for instance, Sykes and Johnston, Nat Biotech 12, 355-59 (1997)), a compacted nucleic acid vector (as described in for instance U.S. Pat. No. 30 6,077,835 and / or WO 00 / 70087), or a plasmid vector such as pBR322, pUC 19 / 18, or pUC 118 / 119. Such nucleic acid vectors and the usage thereof are well known in the art (see, for instance, U.S. Pat. No. 5,589,466 and U.S. Pat. No. 5,973,972). In one embodiment, the DNA comprises an expression control sequence.In one embodiment, the vector is suitable for expression of the peptide of the invention in a bacterial cell. Examples of such vectors include expression vectors such as BlueScript (Stratagene), pIN vectors (Van Heeke & Schuster, 1989, J Biol Chem 264, 5503-5509), pET vectors (Novagen, Madison, Wis.) and the like. In one embodiment, the expression vector may also or alternatively be a vector suitable for expression in a yeast system. Any vector suitable for expression in a yeast system may be employed. Suitable vectors include, for example, vectors comprising constitutive or inducible promoters such as yeast alpha factor, alcoholoxidase and PGH (reviewed in: F. Ausubel et al., ed., 1987, Current Protocols in Molecular Biology, Greene Publishing and Wiley InterScience New York; and Grant et al., 1987, Methods in Enzymol 153, 516-544). In other embodiments, the expression vector is suitable for expression in baculovirus-infected insect cells. (Kost, T; and Condreay, J P, 1999, Current Opinion in Biotechnology 10 (5): 428-33.)Expression control sequences are engineered to control and drive the transcription of genes of interest, and subsequent expression of proteins in various cell systems. Plasmids combine an expressible gene of interest with expression control sequences (i.e. expression cassettes) that comprise desirable elements such as, for example, promoters, enhancers, selectable markers, operators, etc. In an expression vector of the invention, peptide encoding nucleic acid molecules may comprise or be associated with any suitable promoter, enhancer, selectable marker, operator, repressor protein, polyA termination 20 sequences and other expression-facilitating elements.“Promoter” as used herein indicates a DNA sequence sufficient to direct transcription of a DNA sequence to which it is operably linked, i.e., linked in such a way as to permit transcription of the peptide of the invention-encoding nucleotide sequence when the appropriate signals are present. The expression of a peptide-encoding nucleotide sequence may be placed under control of any promoter or enhancer element known in the art. Examples of such elements include strong expression promoters (e.g., human CMV IE promoter / enhancer or CMV major IE (CMV-MIE) promoter, as well as RSV, SV40 late promoter, SL3-3, MMTV, ubiquitin (Ubi), ubiquitin C (UbC), and HIV LTR promoters). In some embodiments, the vector comprises a promoter selected from the group consisting of SV40, CMV, CMV-IE, CMV-MIE, RSV, SL3-3, MMTV, Ubi, UbC and HIV LTR.Nucleic acid molecules of the invention may also be operably linked to an effective poly (A) termination sequence, an origin of replication for plasmid product in E. coli, an antibiotic resistance gene as selectable marker, and / or a convenient cloning site (e.g., a polylinker).Nucleic acids may also comprise a regulatable inducible promoter (inducible, repressable, developmentally regulated) as opposed to a constitutive promoter such as CMV IE (the skilled artisan will recognize that such terms are actually descriptors of a degree of gene expression under certain conditions).Selectable markers are elements well-known in the art. Under the selective conditions, only cells that express the appropriate selectable marker can survive. Commonly, selectable marker genes express proteins, usually enzymes, that confer resistance to various antibiotics in cell culture. In other selective conditions, cells that express a fluorescent protein marker are made visible, and are thus selectable. Embodiments include betalactamase (bla) (beta-lactamantibiotic resistance or ampicillin resistance gene or ampR), bls (blasticidin resistance acetyl transferase gene), bsd (blasticidin-S deaminase resistance gene), bsr (blasticidin-S resistance gene), Sh ble (Zeocin® resistance gene), hygromycin phosphotransferase (hpt) (hygromycin resistance gene), tetM (tetracycline resistance gene or tetR), neomycin phosphotransferase II (npt) (neomycin resistance gene or neoR), kanR (kanamycin resistance gene), and pac (puromycin resistance gene).In certain embodiments, the vector comprises one or more selectable marker genes selected from the group consisting of bla, bls, BSD, bsr, Sh ble, hpt, tetR, tetM, npt, kanR 20 and pac. In other embodiments, the vector comprises one or more selectable marker genes encoding green fluorescent protein (GFP), enhanced green fluorescent protein (eGFP), cyano fluorescent protein (CFP), enhanced cyano fluorescent protein (eCFP), or yellow fluorescent protein (YFP).For the purposes of this invention, gene expression in eukaryotic cells may be tightly regulated using a strong promoter that is controlled by an operatorthat is in turn regulated by a regulatory protein, which may be a recombinant “regulatory fusion protein” (RFP). The RFP consists essentially of a transcription blocking domain, and a ligand-binding domain that regulates its activity. Examples of such expression systems are described in US20090162901 A1 , which is herein incorporated by reference in its entirety.As used herein “operator” indicates a DNA sequence that is introduced in or near a gene in such a way that the gene may be regulated by the binding of the RFP to the operator and, as a result, prevents or allow transcription of the gene of interest, i.e. a nucleotide encoding a peptide of the invention. A number of operators in prokaryotic cells and bacteriophage have been well characterized (Neidhardt, ed., Escherichia coli and Salmonella; Cellular and Molecular Biology 2d. Vol 2 ASM Press, Washington D.C. 1996). These include, but are not limited to, the operator region of the LexA gene of E. coli, which binds the LexA peptide, and the lactose and tryptophan operators, which bind the repressor proteins encoded by the Lad and trpR genes of E. coli. These also include the bacteriophage operators from the lambda PR and the phage P22 ant / mnt genes, which bind the repressor proteins encoded by lambda cl and P22 arc. In some embodiments, when the transcription blocking domain of the RFP is a restriction enzyme, such as Notl, the operator is the recognition sequence for that enzyme. One skilled in the art will recognize that the operator must be located adjacent to, or 3' to the promoter such that it is capable of controlling transcription by the promoter. For example, U.S. Pat. No. 5,972,650, which is incorporated by reference herein, specifies that tetO sequences be within a specific distance from the TATA box. In specific embodiments, the operator is preferably placed immediately downstream of the promoter. In other embodiments, theoperator is placed within 10 base pairs of the promoter. In an exemplary cell expression system, cells are engineered to express the tetracycline repressor protein (TetR) and a protein of interest is placed under transcriptional control of a promoter whose activity is regulated by TetR. Two tandem TetR operators (tetO) are placed immediately downstream of a CMV-MIE promoter / enhancer in the vector.Transcription of the gene encoding the protein of interest directed by the CMV-MIE promoter in such vector may be blocked by TetR in the absence of tetracycline or some other suitable inducer (e.g. doxycycline). In the presence of an inducer, TetR protein is incapable of binding tetO, hence transcription then translation (expression) of the protein of interest occurs. (See, e.g., U.S. Pat. No. 7,435,553, which is herein incorporated by reference in its entirety.)The vectors of the invention may also employ Cre-lox recombination tools to facilitate the integration of a gene of interest into a host genome. A Cre-lox strategy requires at least two components: 1) Cre recombinase, an enzyme that catalyzes recombination between two loxP sites; and 2) loxP sites (e.g. a specific 34-base pair by sequence consisting of an 8-bp core sequence, where recombination takes place, and two flanking 13-bp inverted repeats) or mutant lox sites. (See, e.g. Araki et al., 1995, PNAS 92:160-4; Nagy, A. et al., 2000, Genesis 26:99-109; Araki et al., 2002, Nuc Acids Res 30(19):e103; and US20100291626A1 , all of which are herein incorporated by reference). In another recombination strategy, yeast-derived FLP recombinase may be utilized with the consensus sequence FRT (see also, e.g. Dymecki, S. M., 1996, PNAS 93(12): 6191-6196).As used herein, the term “host cell” includes any cell that is suitable for expressing a recombinant nucleic acid sequence. Cells include those of prokaryotes and eukaryotes (single-cell or multiple-cell), bacterial cells (e.g., strains of E. coli, Bacillus spp., Streptomyces spp., etc.), mycobacteria cells, fungal cells, yeast cells (e.g. S. cerevisiae, S. pombe, P. partoris, P. methanolica, etc.), plant cells, insect cells (e.g. SF-9, SF-21 , baculovirus-infected insect cells, Trichoplusia ni, etc.), non-human animal cells, mammalian cells, human cells, or cell fusions such as, for example, hybridomas or quadromas. In certain embodiments, the cell is a human, monkey, ape, hamster, rat or mouse cell. In other embodiments, the cell is eukaryotic and is selected from the following cells: CHO (e.g. CHO K1 , DXB-11 CHO, Veggie- CHO), COS (e.g. COS-7), retinal cells, Vero, CV1 , kidney (e.g. HEK293, 293 EBNA, MSR 293, MDCK, HaK, BHK21), HeLa, HepG2, WI38, MRC 5, Colo25, HB 8065, HL-60, Jurkat, Daudi, A431 (epidermal), CV-1 , U937, 3T3, L cell, C127 cell, SP2 / 0, NS-0, MMT cell, tumor cell, and a cell line derived from an aforementioned cell. In some embodiments, the cell comprises one or more viral genes, e.g. a retinal cell that expresses a viral gene (e.g. aPER.C6® cell). In some embodiments, the cell is a CHO cell. In other embodiments, the cell is a CHO K1 cell.As used herein, the term “transformed cell of the invention” refers to a host cell comprising a nucleic acid stably integrated into the cellular genome that comprises a nucleotide sequence coding for expression of a peptide of the invention. In another embodiment, the present invention provides a cell comprising a non-integrated (i.e., episomal) nucleic acid, such as a plasmid, cosmid, phagemid, or linear expression element, which comprises a sequence coding for expression of a peptide of the invention. In other embodiments, the present invention provides a cell line produced by stably transfecting a host cell with a plasmid comprising an expression vector of the invention.As used herein, the term “engineered” as applied to a cell means genetically engineered using recombinant DNA technology, and generally involves the step of synthesis of a suitable expression vector (see above) and then transfecting the expression vector into a host cell (generally stable transfection).As used herein, the term “heterologous expression” refers to expression of a nucleic acid in a host cell that does not naturally have the nucleic acid. Insertion of the nucleic acid into the heterologous host is performed by recombinant DNA technology.The term “vasodilation” refers to widening of the blood vessels. It results from relaxation of the muscle cells within the vessel walls. It allows blood flow to increase. Vasodilation of arterial blood vessels decreases blood pressure. Agents (endogenous) that cause vasodilation are called vasodilators. Vasoactive substances are those that either increase or decrease blood pressure and / or heart rate through vasoactivity.The term “hypertension”, is a medical condition in which the blood pressure in the arteries is persistently elevated compared to a normal blood pressure. It is a risk factor for stroke, coronary artery disease, heart failure, chronic kidney disease, atrial fibrillation, peripheral arterial disease, vision loss, and dementia. There is primary and secondary hypertension. Primary hypertension is due to non-specific lifestyle and genetic factors. Secondary hypertension is due to an identifiable cause, such as kidney disease for example. In general, hypertension is blood pressure of 130 / 80 millimeters of mercury (mm Hg) or higher. Stage 1 is when the top number (systolic) is from 130 to 140 mm Hg and the bottom (diastolic) is 80 to 89 mm Hg. Stage 2 is when the top number(systolic) is above 140 mm Hg and the bottom number (diastolic) is above 90 mm Hg.A normal, physiologic blood pressure will vary from person to person. Generally, a normal, physiologic blood pressure is about 120 mm Hg systolic pressure but it can range from 120 to 129 mmHg and / or about 70-80 mm Hg diastolic pressure.The term “ACE inhibitory” when applied to a peptide (including variants and compositions comprising same) means a peptide that is capable of inhibiting the activity of ACE. This may be direct or indirect inhibition. In this context, the peptide is capable of inhibiting ACE activity of FAPGG substrate when compared with an untreated control as determined by the assays described herein.Pulmonary hypertension is a type of high blood pressure that affects the arteries in the lungs and the right side of the heart. One type is called pulmonary arterial hypertension (PAH), in which blood vessels in the lungs are narrowed, blocked or destroyed. Other types include pulmonary hypertension caused by left sided heart disease, pulmonary hypertension caused by lung disease, pulmonary hypertension caused by chronic blood clots and pulmonary hypertension triggered by other health conditions.A sexual disorder or dysfunction is a condition that has a negative impact on the sexual function or the sexual experience. Sexual dysfunction is difficulty experienced by an individual or partners during any stage of normal sexual activity, including physical pleasure, desire, preference, arousal, or orgasm. This includes erectile dysfunction.A “sexual healthy subject” is one that has not been diagnosed with a sexual disorder or dysfunction, i.e. the subject has normal sexual function.The term “sexual function” has normal meaning in the art. It is how the body reacts in different stages of the sexual response cycle. It is an individual’s ability to react sexually or experience pleasure sexually.An “improved sexual function and / or experience” is the improvement in any physiological or psychological condition, or characteristic present in any sexual related activity in a subject at any stage of the response cycle and includes pleasure during sexual experience.“Nitric oxide” is a colourless gas with the formula NO. It is also called nitrogen monoxide.The term “improving muscle status” means improving the muscle health, for example promoting skeletal muscle protein synthesis, skeletal glucose absorption, improving lean tissue mass in therapeutic or non-therapeutic context, promoting muscle recovery generally after activity exercise, or improving muscle performance. The methods or uses may be therapeutic or non-therapeutic. The term “improving lean tissue mass status” should beunderstood to mean increasing lean tissue mass, or inhibiting or preventing the rate of lean tissue mass degradation.“Anti-inflammatory” as applied to a peptide or composition of the invention is one that is capable of significantly reducing the secretion of TN Fa by LPS-stimulated macrophages (compared with untreated LPS-stimulated macrophages) when the macrophages are treated with 50 to 500pg / mL of the composition comprising the peptide as assayed by ELISA, or one that is capable of reducing IL23 expression in cells compared with untreated control as determined by the assays described herein. For example, capable of reducing one or more of at least % compared with untreated control in an anti-inflammatory assay as described herein in cells.“ATP production rate increase” as applied to a peptide or composition of the invention is one that is capable of increasing ATP production via both glycolysis and oxidate phosphorylation in murine C2C12 myoblasts (compared with untreated myoblasts) as determined by the assays described herein when the myoblasts are treated with 5 to 50 pg / ml of the composition of the invention.“Inflammatory disorder” means an immune-mediated inflammatory condition that affects humans and is generally characterised by dysregulated expression of one or more cytokines. Examples of inflammatory disorders include skin inflammatory disorders, inflammatory disorders of the joints, inflammatory disorders of the cardiovascular system, certain autoimmune diseases, lung and airway inflammatory disorders, intestinal inflammatory disorders. Examples of skin inflammatory disorders include dermatitis, for example atopic dermatitis and contact dermatitis, acne vulgaris, and psoriasis. Examples of inflammatory disorders of the joints include rheumatoid arthritis. Examples of inflammatory disorders of the cardiovascular system are cardiovascular disease and atherosclerosis. Examples of autoimmune diseases include Type 1 diabetes, Graves disease, Guillain-Barre disease, Lupus, Psoriatic arthritis, and Ulcerative colitis. Examples of lung and airway inflammatory disorders include asthma, cystic fibrosis, COPD, emphysema, and acute respiratory distress syndrome. Examples of intestinal inflammatory disorders include colitis and inflammatory bowel disease. Other inflammatory disorders include cancer, hay fever, periodontitis, allergies, hypersensitivity, ischemia, depression, systemic diseases, post infection inflammation and bronchitisBrief Description of the FiguresThe invention will be more clearly understood from the following description of an embodiment thereof, given by way of example only, with reference to the accompanying drawings, in which:Figure 1 : ACE Inhibition Assay. Composition A, B and C, (0 - 200 pg / ml) were incubated with 0.125 ll / rnl ACE and 1x FAPGG solution for (A) ACE enzymatic activity taking readings every 30 secs for 30 mins at 340 nm.Figure 2: ACE Inhibition Assay with bioactive peptides of the invention. Synthetic bioactive peptides (A) SEQUENCE ID NO. 1 (B) SEQUENCE ID NO. 2 (C) SEQUENCE ID NO. 10 (D) SEQUENCE ID NO. 4 (E) SEQUENCE ID NO. 3 were incubated with 0.125 U / ml ACE and 1x FAPGG substrate for ACE enzymatic activity taking readings every 30 secs for 30 mins at 340 nm.Figure 3: Cell viability of HAoSMCs following treatment with Composition C was assessed using MTT assay. Composition A (0.05 - 500 pg / ml) treatment did not adversely impact cell viability. (Student’s t-test; *p<0.05 **p<0.01 ***p<0.001 ; data presented are the mean ± SEM of at least 3 independent replicates).Figure 4: Cell viability of HAoSMCs following pep_1853 treatment was assessed using MTT assay. SEQUENCE ID NO. 3 (0.05 - 200 pg / ml) treatment did not adversely impact cell viability. (Student’s t-test; *p<0.05 **p<0.01 ***p<0.001 ; data presented are the mean ± SEM of at least 3 independent replicates).Figure 5: ACE Inhibition Assay. Composition C (0 - 200 pg / ml) were incubated with 0.125 U / ml ACE and 1x FAPGG solution for (A) ACE enzymatic activity taking readings every 30 secs for 30 mins at 340 nm. (B) IC50 calculated using Log[|jg / ml] and percentage ACE inhibition results. Two-way ANOVA Composition C; n=3, ****p=<0.0001.Figure 6: ACE activity inhibition. Captopril and VPP inhibit ACE activity.Figure ?: Peptides exhibiting ACEi activity in-vitro. (A) SEQ ID NO. 15; IC50 124 pg / ml (B) SEQ ID NO. 19; IC50 39 pg / ml (C) SEQ ID NO. 16; IC50 132 pg / ml (D) SEQ ID NO. 20; IC50 70 pg / ml (E) SEQ ID NO. 17; IC50 8 pg / ml (F) SEQ ID NO. 21 ; IC50 15 pg / ml (G) SEQ ID NO. 18; IC50 59 pg / ml (H) SEQ ID NO. 22; IC50 48 pg / ml.Figure 8: Peptides exhibiting ACEi activity in-vitro. (A) SEQ ID NO. 23; IC50 124 pg / ml (B) SEQ ID NO. 24; IC50 114 pg / ml (C) SEQ ID NO.13; IC50 19 pg / ml (D) SEQ ID NO. 25; IC50 202 pg / ml.Figure 9: Peptides exhibiting ACEi activity in-vitro. (A) SEQ ID NO. 3; IC50 29 pg / ml (B) SEQ ID NO. 26; IC50 62 pg / ml (C) SEQ ID NO. 27; IC50 114 pg / ml.Figure 10: ACE Inhibition Assay. SEQ ID 28 (0 - 200 pg / ml) were incubated with 0.125 ll / ml ACE and 1x FAPGG solution for (A) ACE enzymatic activity taking readings every 30 secs for 30 mins at 340 nm.Figure 11 : Composition of an embodiment of the invention has no negative effect on cell viability in THP-1 cells. THP-1 macrophages were left untreated or were treated with the composition (50 - 500 pg / mL), for 24-hours prior to testing in the MTT assay.Figure 12: Composition of an embodiment of the invention inhibits LPS-induced TNF-a secretion from macrophages. THP-1 macrophages were treated with a composition (50-500 pg / mL) for 24 hrs before treating with 100 ng / mL of LPS for 24 hrs. The secretion of TNF-a was quantified by ELISA.Figure 13: The effect of the peptide of SEQUENCE ID NO. 29 on IL signalling. Hek- blue-IL-23 cells were treated with 2 concentrations of the peptide combined with 0.1 ng / mL rlL-23 for24h and effect on IL-23 expression was measured using QUANTI-Blue™ assay from cell supernatants. All treatments were expressed as a percentage of rlL-23 alone. Measurements of recombinant IL-23 (rlL-23; 0.1 ng / mL; black line), neutralising antibody (30 pg / mL; red line), untreated cells (grey bar) are indicated on the graph. Experiments were carried out in triplicates.Figure 14: The effect of the peptide of SEQUENCE ID NO. 28 on IL-23 signalling. Hek- blue-IL-23 cells were treated with 2 concentrations of the peptide combined with 0.1 ng / mL rlL-23 for24h and effect on IL-23 expression was measured using QUANTI-Blue™ assay from cell supernatants. All treatments were expressed as a percentage of rlL-23 alone. Measurements of recombinant IL-23 (rlL-23; 0.1 ng / mL; black line), neutralising antibody (30 pg / mL; red line), untreated cells (grey bar) are indicated on the graph. Experiments were carried out in triplicates.Figure 15: Composition of an embodiment of the invention augments ATP production rate. Murine C2C12 myotubes were treated with the composition. ATP generation by glycolysis and oxidative phosphorylation, were determined using an Agilent Seahorse Analyser.Detailed Description of the InventionThe current invention provides peptides that act as vasodilatorsThe peptide(s) of the invention and a composition(s) comprising one or more peptides of the invention, may be used to treat hypertension, improve sexual function and / or improve or maintain muscle health or recovery.The peptide of the invention has a use to treat hypertension but also as an early intervention strategy for those with early hypertension, or at risk of developing hypertension.There is also a use for ACE inhibition in the exercise industry. ACE inhibition has the effect of vasodilation; hence this allows more blood into muscle tissue. This is beneficial as increased blood flow brings more oxygenated blood and nutrients, while removing breakdown products more effectively.Exercise not only contributes to weight loss, but benefits maximal oxygen consumption, and skeletal muscle blood flow capacity improving vascular homeostasis. Studies have shown that physical active lifestyle delays all-cause mortality and reduces risk for cardiovascular mortality. Therefore, in an embodiment, the peptides of the invention have a cardio-protective benefit.Thus, the peptides can be used in a subclinical threshold for early hypertension, in a normal population for cardio-protective benefits and for use in exercise and endurance sports. The peptides also impact ATP production which provides a use in increasing energy in a subject, or reducing fatigue. The subject may be any subject. The subject may be an otherwise healthy individual. This finds a use in increasing energy during exercise, but also has a use in reducing fatigue in a subject during or post-infection.The peptides comprise (or consist of) a sequence selected from SEQUENCE ID NO. 1 to 14, or therapeutically effective, or bioactive, variants thereof.In an embodiment of the invention the peptide comprises from about 3 to 50 amino acids in length, about 5 to about 50 amino acids in length, preferably up to or about, 6, 8, 10, 15, 20, 25, 30, 35, 40, 45, or 49 amino acids in length, preferably up to or about 14, 15, 16, 17, 18, 19, or 20 amino acids in length. It may be up to 16, up to 20 or up to 30 amino acids in length. It may be from 6 to 20 amino acids in length.The peptides are derived from lentil isolates. In an embodiment, this is Lens culinaris (green lentil). In an embodiment it is red lentil. In an embodiment, it is yellow lentil. It may be a combination. 1Thus, notably, in an aspect of the invention, a composition is provided (composition of the invention) that comprises at least one peptide of the invention. In a preferred embodiment, the composition comprises two peptides of the invention. It may be a combination of any two peptides of the invention. The composition may comprise three peptides, four peptides, or five peptides of the invention. The composition may comprise 6, 7, 8, 9, 10, 11 , 12, 13 or 14 peptides of the invention. In an embodiment, the composition comprises all of the peptides of the invention.In an embodiment, the composition comprises at least a peptide of up to 50 amino acids in length and comprising (or consisting of) SEQUENCE ID NO. 3 or a variant thereof.In an embodiment, the composition comprises at least a peptide of up to 50 amino acids in length and comprising (or consisting of) SEQUENCE ID NO. 22 or a variant thereof. The composition may further comprise one or more peptides of the invention.In an embodiment, the composition comprises (or consists of) one or more peptides selected from the group comprising a peptide comprising (or consisting of) SEQUENCE ID NO. 15, a peptide comprising (or consisting of) SEQUENCE ID NO. 16, a peptide comprising (or consisting of) SEQUENCE ID NO. 17, a peptide comprising (or consisting of) SEQUENCE ID NO. 18, a peptide comprising (or consisting of) SEQUENCE ID NO. 19, a peptide comprising (or consisting of) SEQUENCE ID NO. 20, a peptide comprising (or consisting of) SEQUENCE ID NO. 21 , a peptide comprising (or consisting of) SEQUENCE ID NO. 22, a peptide comprising (or consisting of) SEQUENCE ID NO. 23, a peptide comprising (or consisting of) SEQUENCE ID NO. 13, a peptide comprising (or consisting of) SEQUENCE ID NO. 24, a peptide comprising (or consisting of) SEQUENCE ID NO. 25, a peptide comprising (or consisting of) SEQUENCE ID NO. 3, a peptide comprising (or consisting of) SEQUENCE ID NO. 26, a peptide comprising (or consisting of) SEQUENCE ID NO. 27, a peptide comprising (or consisting of) SEQUENCE ID NO. 28, a peptide comprising (or consisting of) SEQUENCE ID NO. 29 and a peptide comprising (or consisting of) SEQUENCE ID NO. 30, or variants thereof.In an embodiment, the composition comprises (or consists of) a peptide comprising (or consisting of) SEQUENCE ID NO. 15, a peptide comprising (or consisting of) SEQUENCE ID NO. 16, a peptide comprising (or consisting of) SEQUENCE ID NO. 17, a peptide comprising (or consisting of) SEQUENCE ID NO. 18, a peptide comprising (or consisting of) SEQUENCE ID NO. 19, a peptide comprising (or consisting of) SEQUENCE ID NO. 20, a peptide comprising (or consisting of) SEQUENCE ID NO. 21 , a peptide comprising (or consisting of) SEQUENCE ID NO. 22, a peptide comprising (or consisting of) SEQUENCE ID NO. 23, a peptide comprising (or consisting of) SEQUENCE ID NO. 13, a peptide comprising (orconsisting of) SEQUENCE ID NO. 24, a peptide comprising (or consisting of) SEQUENCE ID NO. 25, a peptide comprising (or consisting of) SEQUENCE ID NO. 3, a peptide comprising (or consisting of) SEQUENCE ID NO. 26, a peptide comprising (or consisting of) SEQUENCE ID NO. 27, a peptide comprising (or consisting of) SEQUENCE ID NO. 28, a peptide comprising (or consisting of) SEQUENCE ID NO. 29 and a peptide comprising (or consisting of) SEQUENCE ID NO. 30.In an embodiment, the composition comprises (or consists of) a peptide consisting of SEQUENCE ID NO. 15, a peptide consisting of SEQUENCE ID NO. 16, a peptide consisting of SEQUENCE ID NO. 17, a peptide consisting of SEQUENCE ID NO. 18, a peptide consisting of SEQUENCE ID NO. 19, a peptide consisting of SEQUENCE ID NO. 20, a peptide consisting of SEQUENCE ID NO. 21 , a peptide consisting of SEQUENCE ID NO. 22, a peptide consisting of SEQUENCE ID NO. 23, a peptide consisting of SEQUENCE ID NO. 13, a peptide consisting of SEQUENCE ID NO. 24, a peptide consisting of SEQUENCE ID NO. 25, a peptide consisting of SEQUENCE ID NO. 3, a peptide consisting of SEQUENCE ID NO. 26, a peptide consisting of SEQUENCE ID NO. 27, a peptide consisting of SEQUENCE ID NO. 28, a peptide consisting of SEQUENCE ID NO. 29 and a peptide consisting of SEQUENCE ID NO. 30.In an embodiment, the composition comprises (or consists of) one or more peptides selected from the group comprising a peptide comprising (or consisting of) SEQUENCE ID NO. 3, a peptide comprising (or consisting of) SEQUENCE ID NO. 13, a peptide comprising (or consisting of) SEQUENCE ID NO. 15, a peptide comprising (or consisting of) SEQUENCE ID NO. 16, a peptide comprising (or consisting of) SEQUENCE ID NO. 18, a peptide comprising (or consisting of) SEQUENCE ID NO. 21 , a peptide comprising (or consisting of) SEQUENCE ID NO. 22, a peptide comprising (or consisting of) SEQUENCE ID NO. 23, a peptide comprising (or consisting of) SEQUENCE ID NO. 25, and a peptide comprising (or consisting of) SEQUENCE ID NO. 26, or variants thereof.In an embodiment, the composition comprises (or consists of) a peptide comprising (or consisting of) SEQUENCE ID NO. 3, a peptide comprising (or consisting of) SEQUENCE ID NO. 13, a peptide comprising (or consisting of) SEQUENCE ID NO. 15, a peptide comprising (or consisting of) SEQUENCE ID NO. 16, a peptide comprising (or consisting of) SEQUENCE ID NO. 18, a peptide comprising (or consisting of) SEQUENCE ID NO. 21 , a peptide comprising (or consisting of) SEQUENCE ID NO. 22, a peptide comprising (or consisting of) SEQUENCE ID NO. 23, a peptide comprising (or consisting of) SEQUENCE ID NO. 25, and a peptide comprising (or consisting of) SEQUENCE ID NO. 26.In an embodiment, the composition comprises (or consists of) a peptide consisting of SEQUENCE ID NO. 3, a peptide consisting of SEQUENCE ID NO. 13, a peptide consisting ofSEQUENCE ID NO. 15, a peptide consisting of SEQUENCE ID NO. 16, a peptide consisting of SEQUENCE ID NO. 18, a peptide consisting of SEQUENCE ID NO. 21 , a peptide consisting of SEQUENCE ID NO. 22, a peptide consisting of SEQUENCE ID NO. 23, a peptide consisting of SEQUENCE ID NO. 25, and a peptide consisting of SEQUENCE ID NO. 26.In an embodiment, the composition comprises (or consists of) one or more peptides selected from the group comprising a peptide comprising (or consisting of) SEQUENCE ID NO. 1 , a peptide comprising (or consisting of) SEQUENCE ID NO. 2, a peptide comprising (or consisting of) SEQUENCE ID NO. 3, a peptide comprising (or consisting of) SEQUENCE ID NO. 4, a peptide comprising (or consisting of) SEQUENCE ID NO. 10 and a peptide comprising (or consisting of) SEQUENCE ID No. 11 , or variants thereof.In an embodiment, the composition comprises (or consists of) a peptide comprising (or consisting of) SEQUENCE ID NO. 1 , a peptide comprising (or consisting of) SEQUENCE ID NO. 2, a peptide comprising (or consisting of) SEQUENCE ID NO. 3, a peptide comprising (or consisting of) SEQUENCE ID NO. 4, a peptide comprising (or consisting of) SEQUENCE ID NO. 10 and a peptide comprising (or consisting of) SEQUENCE ID No. 11.In an embodiment, the composition comprises a peptide consisting of SEQUENCE ID NO. 1 , a peptide consisting of SEQUENCE ID NO. 2, a peptide consisting of SEQUENCE ID NO. 3, a peptide consisting of SEQUENCE ID NO. 4, a peptide consisting of SEQUENCE ID NO. 10 and a peptide consisting of SEQUENCE ID No. 11.In an embodiment, the composition comprises (or consists of) one or more peptides selected from the group comprising a peptide comprising (or consisting of) SEQUENCE ID NO. 5, a peptide comprising (or consisting of) SEQUENCE ID NO. 3, a peptide comprising (or consisting of) SEQUENCE ID NO. 6, a peptide comprising (or consisting of) SEQUENCE ID NO. 7, and a peptide comprising (or consisting of) SEQUENCE ID NO. 14, or variants thereof.In an embodiment, the composition comprises (or consists of) a peptide comprising (or consisting of) SEQUENCE ID NO. 5, a peptide comprising (or consisting of) SEQUENCE ID NO. 3, a peptide comprising (or consisting of) SEQUENCE ID NO. 6, a peptide comprising (or consisting of) SEQUENCE ID NO. 7, and a peptide comprising (or consisting of) SEQUENCE ID NO. 14, or variants thereof.In an embodiment, the composition comprises a peptide consisting of SEQUENCE ID NO. 5, a peptide consisting of SEQUENCE ID NO. 3, a peptide consisting of SEQUENCE ID NO. 6, a peptide consisting of SEQUENCE ID NO. 7, and a peptide consisting of SEQUENCE ID NO. 14.In an embodiment, the composition comprises (or consists of) one or more peptides selected from the group comprising a peptide comprising (or consisting of) SEQUENCE ID NO. 12, a peptide comprising (or consisting of) SEQUENCE ID NO. 8, a peptide comprising (or consisting of) SEQUENCE ID NO. 3, a peptide comprising (or consisting of) SEQUENCE ID NO. 13, a peptide comprising (or consisting of) SEQUENCE ID NO. 14, and a peptide comprising (or consisting of) SEQUENCE ID NO. 6, or variants thereof.In an embodiment, the composition comprises (or consists of) a peptide comprising (or consisting of) SEQUENCE ID NO. 12, a peptide comprising (or consisting of) SEQUENCE ID NO. 8, a peptide comprising (or consisting of) SEQUENCE ID NO. 3, a peptide comprising (or consisting of) SEQUENCE ID NO. 13, a peptide comprising (or consisting of) SEQUENCE ID NO. 14, and a peptide comprising (or consisting of) SEQUENCE ID NO. 6, or variants thereof.In an embodiment, the composition comprises a peptide consisting of SEQUENCE ID NO. 12, a peptide consisting of SEQUENCE ID NO. 8, a peptide consisting of SEQUENCE ID NO. 3, a peptide consisting of SEQUENCE ID NO. 13, a peptide consisting of SEQUENCE ID NO. 14, and a peptide consisting of SEQUENCE ID NO. 6.The variant of any one of the sequences SEQUENCE ID NO. 1 to 30, may have 1 to 5 amino acid changes compared with the sequence. In an embodiment, the variant has 1 to 4 amino acid changes compared with the sequence. In one embodiment, the variant has 1 to 3 amino acid changes compared with the sequence. In one embodiment, the variant has 1 to 2 amino acid changes compared with the sequence. In one embodiment, the amino acid change is a conservative amino acid change. In one embodiment, the amino acid change is an amino acid substitution. In one embodiment, the amino acid substitution is a conservative substitution. In one embodiment, the amino acid change is an amino acid addition. In one embodiment, the amino acid change is an amino acid deletion. The change may be at any position of the amino acid sequence. It may be at one or more of position 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12, depending on the length of the amino acid.The amino acid change may be at the terminal end. It may be at the N terminal and / or C terminal. In one embodiment, it is a deletion of one or more amino acids. In an embodiment, it is an addition of one or more amino acids.SEQUENCE ID NO. 5 and 12 are example variants of SEQUENCE ID NO. 1. The amino acid change may be at position 2 and 3 of SEQUENCE ID NO. 1 and / or an addition at the C terminus.SEQUENCE ID NO. 6 is an example variant of SEQUENCE ID NO. 4.SEQUENCE ID NO. 9 and 10 are example variants of SEQUENCE ID NO. 7.SEQUENCE ID NO. 8 and 11 are example variants of SEQUENCE ID NO. 2.SEQUENCE ID NO. 13 and 14 are example variants of SEQUENCE ID NO. 3.Further variants of the peptides of the invention are the following:Variants of SEQUENCE ID NO. 15 includeLFENENGHI (SEQUENCE ID NO.31)ENENGHIR (SEQUENCE ID NO.32)FENENGHIRLI (SEQUENCE ID NO.33)LFENENGHVR (SEQUENCE ID NO.34)ENENGHIRL (SEQUENCE ID NO.35)IFENEHGHIR (SEQUENCE ID NO.36)FENGNGHIR (SEQUENCE ID NO.37)FENENGHI (SEQUENCE ID NO.38)IYENENGHIR (SEQUENCE ID NO.39)ENENGHIRLI (SEQUENCE ID NQ.40)YENENGHIR (SEQUENCE ID NO.41)LYENENGHIR (SEQUENCE ID NO.42)FENENGHIRLL (SEQUENCE ID NO.43)TLFENENGHI (SEQUENCE ID NO.44)ENENGHIRR (SEQUENCE ID NO.45)FENENGHIRL (SEQUENCE ID NO.46)FENEHGHIR (SEQUENCE ID NO.47)FENENGHVR (SEQUENCE ID NO.48)YENENGHIRL (SEQUENCE ID NO.49)FENENGHIRR (SEQUENCE ID NQ.50)LFENENGHIR (SEQUENCE ID NO.51)LFENGNGHIR (SEQUENCE ID NO.52)FENENGHIR (SEQUENCE ID NO.53)ENENGHIRLL (SEQUENCE ID NO.54)FENENGHIRRL (SEQUENCE ID NO.55)FENEHGHIRL (SEQUENCE ID NO.56)LFENENGHIRL (SEQUENCE ID NO.57)LFENENGHIRR (SEQUENCE ID NO.58) FENENGHVRL (SEQUENCE ID NO.59) FENGNGHIRL (SEQUENCE ID NQ.60) TLFENENGHIR (SEQUENCE ID NO.61)Variants of SEQUENCE ID NO. 16 DPNGLHIP (SEQUENCE ID NO.62) IDPNGLHIPS (SEQUENCE ID NO.63) NGLHIPS (SEQUENCE ID NO.64) PNGLHIPS (SEQUENCE ID NO.65) PNGLHIP (SEQUENCE ID NO.66) PNGLHIPSFS (SEQUENCE ID NO.67) NGLHIPSF (SEQUENCE ID NO.68) DPNGLHIPSF (SEQUENCE ID NO.69) PNGLHLPS (SEQUENCE ID NQ.70) DPNGLHIPS (SEQUENCE ID NO.71) PNGLHIPSF (SEQUENCE ID NO.72)Variants of SEQUENCE ID NO. 17VNPRVPEMI (SEQUENCE ID NO.73) LWVNPRVPEM (SEQUENCE ID NO.74) WVNPRVPE (SEQUENCE ID NO.75) VNPRVPEM (SEQUENCE ID NO.76) L WVNPRVPE (SEQUENCE ID NO.77) WVNPRVPEMV (SEQUENCE ID NO.78) VNPRVPEMV (SEQUENCE ID NO.79) WVNPRVPEMIG (SEQUENCE ID NQ.80) VNPRVPEMIG(SEQUENCE ID NO.81) LVNPRVPEM (SEQUENCE ID NO. 82) WVNPRVPEM (SEQUENCE ID NO.83)Variants of SEQUENCE ID NO. 18PDYKPANKL (SEQUENCE ID NO.84)CPDYKPANK (SEQUENCE ID NO.85) TCPDYKPANK (SEQUENCE ID NO.86) PDYKPANKLQ (SEQUENCE ID NO.87) DYKPANK (SEQUENCE ID NO.88) DYKPANKL (SEQUENCE ID NO.89) PDYKPANK (SEQUENCE ID NQ.90) PDYKPSNK (SEQUENCE ID N0.91)Variants of SEQUENCE ID NO. 19 PNYNSRA (SEQUENCE ID NO.92) PHYNSRS (SEQUENCE ID NO.93) PHYNSRA (SEQUENCE ID NO.94) PHYNSR (SEQUENCE ID NO.95) LPHYNSRA (SEQUENCE ID NO.96) PHYNSKA (SEQUENCE ID NO.97) LPHYNSR (SEQUENCE ID NO.98)Variants of SEQUENCE ID NO. 20NPQAGRIKT (SEQUENCE ID NO.99) NPQAGRIKTV (SEQUENCE ID NQ.100) YIPQAGRIKT (SEQUENCE ID NQ.101) IPQAGRIKT (SEQUENCE ID NQ.102) IPQAGRIK (SEQUENCE ID NQ.103) PEAGRIKT (SEQUENCE ID NQ.104) NPQAGRIK (SEQUENCE ID NQ.105) YNPQAGRIKT (SEQUENCE ID NQ.106) PQAGRIKT (SEQUENCE ID NQ.107) QAGRIKT (SEQUENCE ID NQ.108)Variants of SEQUENCE ID NO. 21IYSNKFGR (SEQUENCE ID NQ.109) IYSNKLGK (SEQUENCE ID NQ.110) YSNKFGKL (SEQUENCE ID NO.111) PIYSNKFGK (SEQUENCE ID NO.112)IYSNKFGKFF (SEQUENCE ID N0.113) KYSNKFGK (SEQUENCE ID N0.114) YSNKFGK (SEQUENCE ID N0.115) LYSNKFGK (SEQUENCE ID N0.116) IYSNKFGK (SEQUENCE ID N0.117) IYSNEFGK (SEQUENCE ID N0.118) IYSNKFGKF (SEQUENCE ID N0.119) IYSNNFGK (SEQUENCE ID NQ.120) YSNKFGKF (SEQUENCE ID N0.121) PIYSNKFG (SEQUENCE ID NO.122) PIYSNKFGKF (SEQUENCE ID NO.123) EPIYSNKFGK (SEQUENCE ID NO.124) SPIYSNKFGK (SEQUENCE ID NO.125) IYSNKFGE (SEQUENCE ID NO.126) IYSNKFGN (SEQUENCE ID NO.127) IYSNKFG (SEQUENCE ID NO.128) NPIYSNKFGK (SEQUENCE ID NO.129)Variants of SEQUENCE ID NO. 22PIYSNEFGKF (SEQUENCE ID NO. 130) IYSNKFGNF (SEQUENCE ID NO. 131) IYSNKFGKFFE (SEQUENCE ID NO. 132) PIYSNKFGKFF (SEQUENCE ID NO. 133) PIYSNKLGKF (SEQUENCE ID NO. 134) SPIYSNKFGKF (SEQUENCE ID NO. 135) PIYSNKFGK (SEQUENCE ID NO. 136) IYSNKFGEF (SEQUENCE ID NO. 137) IYSNEFGKFF (SEQUENCE ID NO. 138) IYSNNFGKF (SEQUENCE ID NO. 139) IYSNEFGKF (SEQUENCE ID NO. 140) IYSNKFGKFF (SEQUENCE ID NO. 141) IYSNKFGK (SEQUENCE ID NO. 142) YSNKFGKFF (SEQUENCE ID NO. 143)IYSNKFGKF(SEQUENCE ID NO. 144) PLYSNKFGKF(SEQUENCE ID NO. 145) LYSNKFGKF (SEQUENCE ID NO. 146) YSNKFGKFFE (SEQUENCE ID NO. 147) YSNKFGKF (SEQUENCE ID NO. 148) IYSNKLGKF (SEQUENCE ID NO. 149) PIYSNNFGKF (SEQUENCE ID NO. 150) PIYSNKFGKF (SEQUENCE ID NO. 151) EPIYSNKFGK (SEQUENCE ID NO. 152) IYSNKFGNFL (SEQUENCE ID NO. 153) SPIYSNKFGK (SEQUENCE ID NO. 154) IYSNNFGKFF (SEQUENCE ID NO. 155) IYSNKFGEFY (SEQUENCE ID NO. 156) LYSNKFGKFF (SEQUENCE ID NO. 157) NPIYSNKFGK (SEQUENCE ID NO. 158) EPIYSNKFGKF (SEQUENCE ID NO. 159) NPIYSNKFGKF (SEQUENCE ID NO. 160) PIYSNKFGNF (SEQUENCE ID NO. 161) IYSNKFGNFF (SEQUENCE ID NO. 162)Variants of SEQUENCE ID NO. 23EITPEKNPQLQ (SEQUENCE ID NO. 163) FEITPEKNPQLQ (SEQUENCE ID NO. 164) LEITPEKNPQLQ (SEQUENCE ID NO. 165) ITPEKNPQLQ (SEQUENCE ID NO. 166) ITPEKNPQLQD (SEQUENCE ID NO. 167) ITPEKNPQLQDL (SEQUENCE ID NO. 168) EITPEKNPQLQD (SEQUENCE ID NO. 169)Variants of SEQUENCE ID NO. 13IPVNNPGQ(SEQUENCE ID NO. 170)IPVNRPGQL (SEQUENCE ID NO. 171)IPVNRPGQLQ (SEQUENCE ID NO. 172) VIPVNRPG (SEQUENCE ID NO. 173) IPVNRPG (SEQUENCE ID NO. 174) LAIPVNRPGQ (SEQUENCE ID NO. 175) PVNRPGQL (SEQUENCE ID NO. 176) IPVNRPGQFQ (SEQUENCE ID NO. 177) IPVNRPGQ (SEQUENCE ID NO. 178) IPVNRPGQF (SEQUENCE ID NO. 179) PVNRPGQF (SEQUENCE ID NO. 180) PVNRPGQ (SEQUENCE ID NO. 181) IIPVNRPGQ (SEQUENCE ID NO. 182) AIPVNRPGQF (SEQUENCE ID NO. 183) IPVNKPGQ (SEQUENCE ID NO. 184) AIPVNRPGQL (SEQUENCE ID NO. 185) IPVNRPGK (SEQUENCE ID NO. 186) AIPVNRPG (SEQUENCE ID NO. 187) AIPVNRPGQ (SEQUENCE ID NO. 188)Variants of SEQUENCE ID NO. 24LDWYKGPT (SEQUENCE ID NO. 189) DWYKGPT (SEQUENCE ID NO. 190) WYKGPTL (SEQUENCE ID NO. 191) DWYKGP (SEQUENCE ID NO. 192) DWYKGPTL (SEQUENCE ID NO. 193) LDWYKGP (SEQUENCE ID NO. 194) WYKGPT (SEQUENCE ID NO. 195)Variants of SEQUENCE ID NO. 25GLHLPSYSPSP (SEQUENCE ID NO. 196) GLHLPSFSPSPQ (SEQUENCE ID NO. 197) LHLPSYSPYP (SEQUENCE ID NO. 198) LHIPSFSPSPQ (SEQUENCE ID NO. 199)LHLPSYSPYPQ (SEQUENCE ID NO. 200) LHLPSFSPSPQ (SEQUENCE ID NO. 201) HLPSYSPSP (SEQUENCE ID NO. 202) LHLPSYSNAPQ (SEQUENCE ID NO. 203) LHLPSYSPSPQ (SEQUENCE ID NO. 204) LHLPSYSPSP (SEQUENCE ID NO. 205) HLPSYSPSPQL (SEQUENCE ID NO. 206) GLHLPSYSPYP (SEQUENCE ID NO. 207) LPSYSPSPQL (SEQUENCE ID NO. 208) LPSYSPSPQLI (SEQUENCE ID NO. 209) LHLPSYSPS (SEQUENCE ID NO. 210) NGLHLPSYSPSPQ (SEQUENCE ID NO. 211) HLPSFSPSPQ (SEQUENCE ID NO. 212) HLPSYSPYPQM (SEQUENCE ID NO. 213) HLPSYSPYPQ (SEQUENCE ID NO. 214) NGLHLPSYSPS (SEQUENCE ID NO. 215) GLHLPSYSPYPQ (SEQUENCE ID NO. 216) LHLPSYSPYPQM (SEQUENCE ID NO. 217) LHMPSYSPYPQ (SEQUENCE ID NO. 218) GLHLPSYSPSPQL (SEQUENCE ID NO. 219) GLHLPSYSPS (SEQUENCE ID NO. 220) LHLPSYSPSPQLI (SEQUENCE ID NO. 221) GLHLPSYSPSPQ (SEQUENCE ID NO. 222) HLPSYSPSPQ (SEQUENCE ID NO. 223) LHLPSYSPSPQL(SEQUENCE ID NO. 224) HLPSFSPSPQL (SEQUENCE ID NO. 225) LPSYSPSPQ (SEQUENCE ID NO. 226) LHLPSYSPYPR (SEQUENCE ID NO. 227) GLHLPSFSPSP (SEQUENCE ID NO. 228) LHLPSFSPSPQL (SEQUENCE ID NO. 229) NGLHLPSYSPSP (SEQUENCE ID NO. 230)Variants of SEQUENCE ID NO. 3VNRPGQL (SEQUENCE ID NO. 231) IPVNRPG (SEQUENCE ID NO. 232) PVNRPGQL (SEQUENCE ID NO. 233) IPVNRPGQ (SEQUENCE ID NO. 234) PVNRPGQF (SEQUENCE ID NO. 235) PVNRPGQ (SEQUENCE ID NO. 236) VNRPGQ (SEQUENCE ID NO. 237) VNRPGQF (SEQUENCE ID NO. 238) PVNRPGK (SEQUENCE ID NO. 239) PVNKPGQ (SEQUENCE ID NO. 240)Variants of SEQUENCE ID NO. 26KFFEITPEKNPQ (SEQUENCE ID NO. 241) EITPEKNPQ (SEQUENCE ID NO. 242) EITPKKNPQL (SEQUENCE ID NO. 243) FEITPEKNQQ (SEQUENCE ID NO. 244) FFEITPEKNQ (SEQUENCE ID NO. 245) ITPEKNPQL (SEQUENCE ID NO. 246) FYEITPEKNP (SEQUENCE ID NO. 247) EITPEKSPQ (SEQUENCE ID NO. 248) HEITPEKNPQL (SEQUENCE ID NO. 249) FFEITPKKNPQ (SEQUENCE ID NO. 250) EITPEKNQQ (SEQUENCE ID NO. 251) NFFEITPEKNP (SEQUENCE ID NO. 252) FEITPERNPQ (SEQUENCE ID NO. 253) WYEITPEKNPQ (SEQUENCE ID NO. 254) EITPEKNP (SEQUENCE ID NO. 255) WYEITPEKNP (SEQUENCE ID NO. 256) WFEITPERNPQ (SEQUENCE ID NO. 257) YEITPEKNPQL (SEQUENCE ID NO. 258) YEITPEKNP (SEQUENCE ID NO. 259)FEITPKRNPQ (SEQUENCE ID NO. 260) FEITPERNPQL (SEQUENCE ID NO. 261) FEITPEKSPQ (SEQUENCE ID NO. 262) KFFEITPEKNP (SEQUENCE ID NO. 263) FEITPERNP (SEQUENCE ID NO. 264) YEITPEKNPQ (SEQUENCE ID NO. 265) KFFEITPEKN (SEQUENCE ID NO. 266) FEITPEKSPQL (SEQUENCE ID NO. 267) EITPEKNPQLR (SEQUENCE ID NO. 268) LFEITPEKN (SEQUENCE ID NO. 269) EITPKKNPQ (SEQUENCE ID NO. 270) FEITPEKNQ (SEQUENCE ID NO. 271) EITPEKNPQLQ (SEQUENCE ID NO. 272) FFEITPEKNPQL (SEQUENCE ID NO. 273) LFEITPEKNPQL (SEQUENCE ID NO. 274) ITPEKNPQLR (SEQUENCE ID NO. 275) FFEITPEKNP (SEQUENCE ID NO. 276) FEITPEKN (SEQUENCE ID NO. 277) KLFEITPEKN (SEQUENCE ID NO. 278) MHEITPEKNPQ (SEQUENCE ID NO. 279) HEITPEKNPQ (SEQUENCE ID NO. 280) FEITPEKNPQLK (SEQUENCE ID NO. 281) FEITPKKNPQ (SEQUENCE ID NO. 282) FEITPEKNPQLQ (SEQUENCE ID NO. 283) FEITPEKNPQ (SEQUENCE ID NO. 284) FFEITPEKSP (SEQUENCE ID NO. 285) FYEITPEKNPQ (SEQUENCE ID NO. 286) FEITPEKNP (SEQUENCE ID NO. 287) NFFEITPEKNPQ (SEQUENCE ID NO. 288) LFEITPEKNPQ (SEQUENCE ID NO. 289) FEITPEKNPQLR (SEQUENCE ID NO. 290) LFEITPEKNP (SEQUENCE ID NO. 291) EITPEKNQQL (SEQUENCE ID NO. 292) EITPEKNPQLK (SEQUENCE ID NO. 293)YEITPKKNPQ (SEQUENCE ID NO. 294) NFFEITPEKN (SEQUENCE ID NO. 295) FFEITPEKNQQ (SEQUENCE ID NO. 296) LEITPEKNPQ (SEQUENCE ID NO. 297) FEITPEKNPQL (SEQUENCE ID NO. 298) FEITPKKNP (SEQUENCE ID NO. 299) FFEITPKKNP (SEQUENCE ID NO. 300) EITPEKSPQL (SEQUENCE ID NO. 301) FFEITPEKNPQ (SEQUENCE ID NO. 302) FFEITPEKN (SEQUENCE ID NO. 303) ITPEKNPQLQ (SEQUENCE ID NO. 304) FEITPKKNPQL (SEQUENCE ID NO. 305) WFEITPERNP (SEQUENCE ID NO. 306) EITPEKNPQL (SEQUENCE ID NO. 307) FEITPEKNQQL (SEQUENCE ID NO. 308) ITPEKNPQLK (SEQUENCE ID NO. 309) ITPEKNPQ (SEQUENCE ID NO. 310) FELTPEKNQQ (SEQUENCE ID NO. 311)Variants of SEQUENCE ID NO. 27NGIYAPHW (SEQUENCE ID NO.312) RNGIYAP (SEQUENCE ID NO.313) NGIYAPY (SEQUENCE ID NO.314) GIYAPHW (SEQUENCE ID NO.315) NGIYSPH (SEQUENCE ID NO.316) NGINAPH (SEQUENCE ID NO.317) RNGIYAPH (SEQUENCE ID NO.318) NGIYAPH (SEQUENCE ID NO.319) NGIMAPH (SEQUENCE ID NQ.320) NGITAPH (SEQUENCE ID NO.321) NGIYAP (SEQUENCE ID NO.322)Variants of SEQUENCE ID NO. 28WNPNHP (SEQUENCE ID NO.323) TWNPNHPE (SEQUENCE ID NO.324) NPNHPEL (SEQUENCE ID NO.325) WNPNHPEL (SEQUENCE ID NO.326) NPNHPE(SEQUENCE ID NO.327) WNPNNPE (SEQUENCE ID NO.328) WNPNHPE (SEQUENCE ID NO.329) TWNPNHP (SEQUENCE ID NQ.330)Variants of SEQUENCE ID NO. 29TWNPNHPEL (SEQUENCE ID NO.331) TWNPNHPELK (SEQUENCE ID NO.332) TETWNPNHPELK (SEQUENCE ID NO.333) TETWNPNHPE (SEQUENCE ID NO.334) TWNPNHPE (SEQUENCE ID NO.335) ITETWNSNHPE (SEQUENCE ID NO.336) TWNPNHPELR (SEQUENCE ID NO.337) LTETWNPNH (SEQUENCE ID NO.338) LTETWNPNHPE (SEQUENCE ID NO.339) GLTETWNPNHP (SEQUENCE ID NQ.340) TETWNPNHPELR (SEQUENCE ID NO.341) ETWNPNHPELK (SEQUENCE ID NO.342) TETWNPNNPE (SEQUENCE ID NO.343) TWNPNHPELQ (SEQUENCE ID NO.344) GLTETWNPNH (SEQUENCE ID NO.345) TETWNPNNP (SEQUENCE ID NO.346) TETWNPNNPEL (SEQUENCE ID NO.347) ETWNPNNPEL (SEQUENCE ID NO.348) LTETWNPNHP (SEQUENCE ID NO.349) ETWNPNHPELQ (SEQUENCE ID NQ.350) LTETWNPNNPE (SEQUENCE ID NO.351) ETWNPNHP (SEQUENCE ID NO.352) LTETWNPNHPEL (SEQUENCE ID NO.353)ETWNPNNPE (SEQUENCE ID NO.354)ETWNPNHPELR (SEQUENCE ID NO.355)TETWNPNHPELQ (SEQUENCE ID NO.356)TETWNPNHPEL (SEQUENCE ID NO.357)ETWNPNHPE (SEQUENCE ID NO.358)TETWNPNHP (SEQUENCE ID NO.359)TETWNPNH (SEQUENCE ID NQ.360)GLTETWNPNHPE (SEQUENCE ID NO.361) ETWNPNHPEL (SEQUENCE ID NO.362)Variants of SEQUENCE ID NO. 30ASFNTKYETIER (SEQUENCE ID NO.363)EASFNTDYETIER (SEQUENCE ID NO.364)SFNTDYETIER (SEQUENCE ID NO.365)ASFNTDYETIER (SEQUENCE ID NO.366)The peptides of the invention are used in the composition of this invention at therapeutically effective concentrations to achieve the desired effect; in a preferred form with regards to the total weight of the composition, between 0.00000001% (in weight) and 20% (in weight); preferably between 0.000001% (in weight) and 15% (in weight), more preferably between 0.0001% (in weight) and 10% (in weight) and even more preferably between 0.0001% (in weight) and 5% (in weight). Ideally, the peptides of the present invention are preferably used from about 0.00001% w / w to about 0.5% w / w [0.1 to 5000 ppm], and more preferably from 0.00005 w / w to about 0.05 w / w [0.5 to 500 ppm], and most preferably from about 0.0001 w / w to about 0.01 w / w of the composition [1 to 100 ppm]. Ideally, the peptides of the present invention are preferably used from about 0.0001% w / w to about 0.004% w / w of the composition.Preferably, the compositions may be for oral administration. For example, as a dietary supplement or a nutritional supplement. It will be appreciated that it may be in any suitable form.The composition may be a food supplement.The invention may be a food comprising a peptide or composition of the invention.A peptide or a composition of the invention may be adapted for topical, oral, rectal, parenteral, intramuscular, intraperitoneal, intra-arterial, intrabronchial, subcutaneous, intradermal, intravenous, nasal, vaginal, buccal or sublingual routes of administration.The composition of the invention may be presented, prepared and / or administered in a variety of suitable forms. Such forms include, for example, but are not limited to, liquid, semi-solid and solid dosage forms, such as liquid solutions (e.g., injectable and infusible solutions), dispersions or suspensions, emulsions, microemulsions, tablets, pills, powders, granules (granular form), liposomes, dendrimers and other nanoparticles, microparticles, capsules, suppositories and pressed into tablet form. It will be appreciated that the form may depend on the intended mode of administration, the nature of the composition or combination, and therapeutic application or other intended use. Formulations also can include, for example, powders, pastes, ointments, jellies, waxes, oils, lipids, lipid (cationic or anionic) containing vesicles, DNA conjugates, anhydrous absorption pastes, oil-in-water and water-in-oil emulsions, emulsions, carbowax (polyethylene glycols of various molecular weights), semisolid gels, and semi-solid mixtures containing carbowax.In some embodiments of the current invention, the composition may be delivered via any one of liposomes, mixed liposomes, oleosomes, niosomes, ethosomes, millicapsules, capsules, macrocapsules, nanocapsules, nanostructured lipid carriers, sponges, cyclodextrins, vesicles, micelles, mixed micelles of surfactants, surfactant-phospholipid mixed micelles, millispheres, spheres, lipospheres, particles, nanospheres, nanoparticles, milliparticles, solid nanopartciles as well as microemulsions including water-in-oil microemulsions with an internal structure of reverse micelle and nanoemulsions microspheres, microparticles.A variety of methods are available for preparing liposomes. See, e.g., Szoka et al., Ann. Rev. Biophys. Bioeng. 9:467 (1980), U.S. Pat. Nos. 4,186,183, 4,217,344, 4,235,871 , 4,261 ,975, 4,485,054, 4,501 ,728, 4,774,085, 4,837,028, 4,235,871 , 4,261 ,975, 4,485,054, 4,501 ,728, 4,774,085, 4,837,028, 4,946,787, PCT Publication No. WO 91 / 17424, Deamer & Bangham, Biochim. Biophys. Acta 443:629-634 (1976); Fraley, et al., PNAS 76:3348-3352 (1979); Hope et al., Biochim. Biophys. Acta 812:55-65 (1985); Mayer et al., Biochim. Biophys. Acta 858:161- 168 (1986); Williams et al., PNAS 85:242-246 (1988); Liposomes (Ostro (ed.), 1983, Chapter 1); Hope et al., Chem. Phys. Lip. 40:89 (1986); Gregoriadis, Liposome Technology (1984) and Lasic, Liposomes: from Physics to Applications (1993)). Suitable methods include, for example, sonication, extrusion, high pressure / homogenization, microfluidization, detergent dialysis, calcium-induced fusion of small liposome vehicles and ether fusion methods, all of which are well known in the art.The delivery system used in the current invention may be adapted to achieve a greater penetration of the compound and / or peptides of the invention. This may improve pharmacokinetic and pharmacodynamics properties. The delivery system may be a sustained release system wherein the compound or peptide of the invention is gradually released during a period of time and preferably with a constant release rate over a period of time. The delivery systems are prepared by methods known in the art. The amount of peptide contained in the sustained release system will depend on where the composition is to be delivered and the duration of the release as well as the type of the condition, disease and / or disorder to be treated or cared for.The composition may be a pharmaceutical composition. In an embodiment of the invention the composition may further comprise at least one pharmaceutically acceptable excipient. Excipient may be used interchangeably with functional ingredient or additive. It will be understood that although a peptide or a composition of the current invention can be administered alone, they will generally be administered in admixture with a pharmaceutical excipient. Pharmaceutically acceptable excipient are well known in the art and any known excipient. Examples of suitable excipients are disclosed herein.Preferably any excipient included is present in trace amounts. The amount of excipient included will depend on numerous factors, including the type of excipient used, the nature of the excipient, the amount of active or peptide in the composition and / or the intended use of the composition. The nature and amount of any excipient should not unacceptably alter the benefits of the peptides of this invention.In an embodiment of the invention, the composition may further comprise one or more additional ingredients. The composition of the invention may be administered consecutively, simultaneously or sequentially with the one or more other additional agents. Such additional ingredients may be those of benefit to include in a composition formulated in a particular way, e.g. for oral administration, or of benefit depending on the intended use of the composition, e.g. anti-hypertension. The additional ingredient may be active or functional or both.Advantageously, a peptide or composition of the invention may be used as a sole means of promoting the beneficial effect intended, e.g. anti-hypertension, or may be used in combination with other similarly-directed compositions or agents, or as a component of a larger composition.In a particular embodiment, a peptide or composition is to be administered in combination with one or more other active agents, for example, existing anti-hypertension agents, or pharmacological enhancers available on the market. The other active agents may be agentsthat provide a different and / or complementary health benefit. Examples include one or more vitamins and / or minerals. In such cases, the peptide(s) or composition of the invention may be administered consecutively, simultaneously, or sequentially with the one or more other active agents.In an embodiment, the additional ingredient or active agent is one for muscle health and / or recovery. Not to be bound my theory, but it is considered that the peptides and / or compositions of the current invention can augment the blood supply to muscles and thus delivery such ingredients or actives more efficiently. This can also be applied to any additional ingredient or active agent that requires systemic application.It will be appreciated that a plurality of additional ingredients may be added. The amount of the additional ingredient may be from about 0.001% to about 50% weight of the composition, preferably, about 0.01% to about 20%, preferably about 0.1 % to about 10%, about 0.5% to about 10%, about 1% to about 5%, preferably 2% weight of the composition. The amount of additional ingredient included will depend on numerous factors, including the type of additional ingredient used, the nature of the additional ingredient, the component(s) of the composition, the amount of active or peptide in the composition and / or the intended use of the composition. The nature and amount of any additional ingredient should not unacceptably alter the benefits of the peptides of this invention.The composition of the invention may be alcohol free.It is to be understood that an ingredient that is considered to be an “active” ingredient in one product may be a “functional” or “excipient” ingredient in another and vice versa. It will also be appreciated that some ingredients play a dual role as both an active ingredient and as a functional or excipient ingredient.In preferred embodiments, repeated use of the peptide(s) or composition is provided.The invention also comprises a food product comprising a peptides of the invention, or a composition of the invention. In a preferred embodiment, the food product is for human consumption.The composition of the invention may be a comestible product. It may be a food or beverage product.In one embodiment the comestible product is a beverage. In one embodiment the comestible product is a bakery product. In one embodiment the comestible product is a dairy product. In one embodiment the comestible product is a snack product. In one embodiment the comestible product is a baked extruded food product. In one embodiment the comestibleproduct is powdered milk. In one embodiment the comestible product is an infant formula product. In one embodiment the comestible product is a confectionary product. In one embodiment the comestible product is a yoghurt. In one embodiment the comestible product is a yoghurt drink. In one embodiment the comestible product is an ice cream product. In one embodiment the comestible product is a frozen food product. In one embodiment the comestible product is a breakfast cereal. In one embodiment the comestible product is a bread. In one embodiment the comestible product is a flavoured milk drink. In one embodiment the comestible product is a confectionary bar. In one embodiment the comestible product is a tea or tea product. In one embodiment the comestible product is a based extruded snack product. In one embodiment the comestible product is a fried snack product. In one embodiment the comestible product is a nutritional supplement. In one embodiment the comestible product is a sports nutritional product. In one embodiment the comestible product is a baby food product. In one embodiment the comestible product is a speciality food product for immunocompromised individuals. In one embodiment the comestible product is a food for geriatric patients. In one embodiment the comestible product is an energy bar or food bar. In one embodiment the comestible product is a powdered drink mix.In relation to a beverage product, notably in an embodiment, it is selected from an alcoholic beverage, e.g. an alcoholic beer, a non-alcoholic beverage; mineral and / or aerated waters; fruit beverages and fruit juices.In one embodiment, the composition comprises 0.001 to 1.0% of the food product (w / w). In one embodiment, the composition comprises 0.005 to 0.5% of the food product (w / w). In one embodiment, the composition comprises 0.005 to 0.1 % of the food product (w / w). In one embodiment, the composition comprises 0.01 to 0.03% of the food product (w / w). In one embodiment, the composition comprises about 0.02% of the food product (w / w).The composition may be provided in a solid dosage form with specific controlled release characteristics. It may be layered dosage form, with each layer having unique release or dissolution characteristics.The invention will now be described with reference to specific Examples. These are merely exemplary and for illustrative purposes only: they are not intended to be limiting in any way to the scope of the monopoly claimed or to the invention described. These examples constitute the best mode currently contemplated for practicing the invention.EXAMPLESMETHODOLOGYACE InhibitionAngiotensin-converting enzyme (ACE) is an enzyme that plays a central role in the renin- angiotensin-aldosterone system (RAAS), a signalling pathway in the body that regulates blood pressure. ACE converts angiotensin I to angiotensin II, which in turn acts as a vasoconstrictor to thus increase blood pressure. The ACE-inhibitory effects of the peptides and composition of the invention, were assessed using a cell-free kinetic assay.ACE inhibition (ACEi) was measured using N-[3-(2-furyl) acryloyl]-Phe-Gly-Gly (FAPGG), a synthetic substrate of ACE. Briefly, here ACE was plated in the presence of increasing concentrations of the composition and peptides. This was followed by the addition of FAPGG, after which measurements were taken every 30 secs for 30 mins at 340 nm using a CLARIOstar BMG Labtech plate reader. Captopril was used as a positive control.Composition A contains a peptide of SEQ ID NO. 8, a peptide of SEQ ID No. 3 and a peptide of SEQ ID NO. 6.Composition B contains a peptide of SEQ ID NO. 5, a peptide of SEQ ID No. 3, a peptide of SEQ ID NO. 6 and a peptide of SEQ ID NO. 7.Composition C contains a peptide of SEQ ID NO. 1 , a peptide of SEQ ID No. 2, a peptide of SEQ ID NO. 3, a peptide of SEQ ID NO. 4 and a peptide of SEQ ID NO. 7.For synthetically produced bioactive peptides, all concentrations for ACEi assays are given as micromolar (pM), these values are based on the molar concentrations of each peptide at 5 - 100 pg / ml.Toxicity StudiesAn MTT assay was used to determine whether the composition and peptides of the invention were toxic to cells upon treatment. HAoSMC, Caco-2,HepG2 or THP-1 cells were seeded in 96 well plates (1x105cells / well) and treated with the composition or peptide (0.05 - 500 pg / ml). Cells were treated for 15 and 180 mins or 24 hrs with HAoSMC, Caco-2 / HepG2 or THP-1 cells respectively before the well contents were removed and replaced with MTT reagent (0.5 mg / ml). The cells were treated with an MTT reagent for 2 hrs at 37°C, 95% humidity and 5% CO2. MTT is a tetrazolium salt which is converted to formazan via succinate tetrazolium from the sarcoplasm reticulum in the mitochondria in viable cells only. The formazan salt is insoluble but becomes soluble in 100% DMSO. MTT reagent is removed from the cells and replacedwith 100% DMSO for 5 mins while shaken on a plate shaker. The plate is read using a CLARIOstar BMG Labtech plate reader at 560 nm. The generated optical density values are converted to % with untreated cells set at 100%. The inclusion of a DMSO control highlights the % cell death.Inflammation AssayThe secretion of TNF-a from LPS stimulated THP-1 cells assessed by ELISA (BioLegend, San Diego, California, USA) according to manufacturer’s instructions. To differentiate monocyte precursors into macrophages, THP-1 cells were seeded in 96-well plates and treated with 100 nM phorbol-12-myristate-13-acetate (PMA; Sigma-Aldrich, St Louis, MO, USA) for 72 h at 37° C, 5% CO2. After incubation, non-attached cells were aspirated, and adherent cells were treated with lentil protein hydrolysate (50 - 500 pg / mL) in triplicate. Following incubation for 24 hrs, lipopolysaccharide (LPS) from Escherichia coli O127:B8 (Sigma-Aldrich, St Louis, MO, USA) was added at 100 ng / mL for 24 hrs at 37° C, 5% CO2. Cell supernatants were collected, and assayed for the release of TNF-a by ELISA.HK-Blue cells are genetically modified to respond to IL-23 protein and secrete SEAP in a dose dependent manner. QUANTI-Blue™ Solution (InvivoGen, Toulouse) was added to the treated supernatant and a colorimetric change determined any alkaline phosphatase (AP) activity (D. S. Leventhal etal., “Immunotherapy with engineered bacteria by targeting the STING pathway for anti-tumor immunity,” Nat. Commun., vol. 11 , no. 1 , pp. 1-15, 2020). Prior to use in the assay, cells were cultured through at least two rounds of selection antibiotic treatment (Blasticidin, per manufacturers instruction) to ensure all cells retained the required SEAP plasmid with relevant selection antibiotic gene also. The desired concentrations of the peptides and compositions, relative positive controls and ligands were combined with rlL-23 (0.1 ng / mL) and incubated at 37°C for 30 minutes before use. Cells were added at a density of 50,000 cells / well into wells containing the treatments / controls to ensure the correct final concentrations of the reagents and were incubated at 37°C in 5 % CO2 for 24 hours. The following day, 100 mL of QUANTI-Blue™ Solution was prepared by adding 1 mL of QB reagent and 1 mL of QB buffer to 98 mL of sterile autoclaved deionised water in a sterile glass bottle or flask according to manufacturer’s instructions. It was mixed well by vortexing and incubated at room temperature for 10 minutes before use. 40 pL of cell supernatants were collected from each well directly from the 96-well TC plate from day 1 and placed into a new sterile 96-well plate, to which 160pL of QUANTI-Blue™ medium was dispensed per well on top of collected cell supernatants. This plate was incubated at 37°C for two hours, after which the absorbance at 650nm was measured using a microplate reader (Clariostar, BMG Labtech, Offernberg, Germany).The effect of the synthetic peptides and the composition on the IL-17A / IL-23 / TH17 signalling axis was assessed using the QUANTI-Blue™ primary screening assay.ATP Production Rate AssayMurine C2C12 myoblasts were seeded in XFe 96 well Seahorse plates (Agilent, Santa Clara, California) (2500 cells / well) and allowed to grow for 48 hours, Cells were then differentiated into myotubes using differentiation media containing 2% horse serum. The media was replaced daily for 7 consecutive days. Myotube formation was confirmed via observation under a microscope prior to overnight incubation in starvation media. ATP Production was determined using a Seahorse ATP Rate Assay Kit (Agilent). The cells were stimulated with lentil protein hydrolysate in XFe Seahorse RPMI for 60 minutes at 37C in a non-CO 2 incubator. Fresh XFe Seahorse RPMI media was applied to the cells and ATP production (via both glycolysis and oxidative phosphorylation) was assessed with the addition of Oligomycin and Rotenone + Antimycin A, and the monitoring of both the Extra Cellular Acidification Rate (ECAR) the Oxygen Consumption Rate (OCR) using an Agilent Seahorse Analyser.RESULTSACEi bioactivity of Composition A, B and C and cell viability studyAs shown in Figure 1 , ACEi bioactivity of Composition A (Figure 1 A), Composition B (Figure1 B) and Composition C (Figure 1 C) was compared to known ACE inhibitors currently available on the market; the synthetic drug Captopril and a known casein-derived ACE inhibitor VPP (Hernandez-Ledesma et al., 2007; Haque and Chand, 2008; Henda et al., 2013). Following treatment with Composition A - C (5 - 200 pg / ml), a dose-dependent % inhibition of ACE was recorded.As shown in Figure 2, ACEi bioactivity of SEQ. ID NO. 1 (Figure 2 A), SEQ. ID NO. 5 (Figure2 B), SEQ. ID NO. 3 (Figure 2C), SEQ. ID NO. 4 (Figure 2 D), SEQ. ID NO. 2 (Figure 2 E) was compared to known ACE inhibitors currently available on the market; either the synthetic drug Captopril, a known casein-derived ACE inhibitor VPP or FAPGG (a synthetic cromogenic substrate for angiotensin converting enzyme (ACE) determination) (Hernandez-Ledesma et al., 2007; Haque and Chand, 2008; Henda etal., 2013). Following treatment with SEQ. ID NO. 1 - 5, a dose-dependent % inhibition of ACE was recorded.As shown in Figure 3, cell viability of HAoSMCs following Composition C treatment was assessed using MTT assay. Composition C (0.05 - 500 pg / ml) treatment did not adversely impact cell viability. (Student’s t-test; *p<0.05 **p<0.01 ***p<0.001 ; data presented are the mean ± SEM of at least 3 independent replicates).As shown in Figure 4, cell viability of HAoSMCs following SEQ. ID NO. 2 treatment was assessed using MTT assay. SEQ. ID NO. 2 (0.05 - 200 pg / ml) treatment did not adversely impact cell viability. (Student’s t-test; *p<0.05 **p<0.01 ***p<0.001 ; data presented are the mean ± SEM of at least 3 independent replicates).As shown in Figure 5, ACE inhibitory bioactivity of Composition C was compared to Amealpeptide. Amealpeptide is a known peptide in the art (T. Nakamura et al.: Casein hydrolysate containing Val-Pro-Pro and lle-Pro-Pro improves central blood pressure and arterial stiffness in hypertensive subjects: A randomized, double-blind, placebo-controlled trial. Atherosclerosis, 219, 298-303 (2011); C. Suzuki et al.: Effects of lactic casein-derived peptides Val-Pro-Pro and lle-Pro-Pro on vascular endothelial functions and arterial stiffness in menopausal animal subjects. 46th Annual Scientific Meeting of the Japan Atherosclerosis Society (2014). Composition C showed a higher % inhibition compared with the activity of Amealpeptide across all concentrations tested. There results show a higher potency for ACEi with Composition C compared to Amealpeptide.ACEi AssayThe ACEi assay is based on a kinetic reaction and measures the absorbance of ACE substrate, FAPGG at 340 nm and its hydrolysed products, FAP and GG, in the presence of ACE. The result output is “% inhibition” therefore the uninhibited yields no result as there is no ACE, while the positive controls Captopril and VPP, known inhibitors of ACE, yield % decreases of 60-90% (Figure 6).The peptides were tested in-vitro in the ACEi assay and the results illustrating the activity for peptides of SEQ ID 3, 13 and 15 to 28 are shown in Figures 7 to 10.Cellular ViabilityThe viability of THP-1 cells was not affected after 24 hours treatment with the composition of an embodiment of the invention (50 - 500 pg / mL) in an MTT assay (Figure 11).The composition has a peptide of SEQ ID NO.3, SEQ ID NO.13, SEQ ID NO.15, SEQ ID NO.16, SEQ ID NO.17, SEQ ID NO.18, SEQ ID NO. 19, SEQ ID NQ.20, SEQ ID NO.21 , SEQ ID NO.22, SEQ ID NO.23, SEQ ID NO.24, SEQ ID NO.25, SEQ ID NO.26, SEQ ID NO.27, SEQ ID NO.28, SEQ ID NO.29 and SEQ ID NO. 30.Untreated cells were considered 100% viable, therefore the effects on cellular viability in the treated cells were calculated as a percent of the untreated control cells. This data suggests that the composition does not have any adverse effect on cell viability in vitro, at the dose range used.Anti-Inflammatory PropertiesTHP-1 cells were differentiated into macrophages by seeding in 96-well plates and treating with 100 nM phorbol-12-myristate-13-acetate (PMA) for 72 hours at 37° C, 5% CO2. After incubation, non-attached cells were aspirated, and adherent cells were treated with a composition of the invention (50 - 500 pg / mL) in triplicate.The composition has a peptide of SEQ ID NO.3, SEQ ID NO.13, SEQ ID NO.15, SEQ ID NO.16, SEQ ID NO.17, SEQ ID NO.18, SEQ ID NO. 19, SEQ ID NQ.20, SEQ ID NO.21 , SEQ ID NO.22, SEQ ID NO.23, SEQ ID NO.24, SEQ ID NO.25, SEQ ID NO.26, SEQ ID NO.27, SEQ ID NO.28, SEQ ID NO.29 and SEQ ID NO. 30.Following incubation for 24 hours, LPS from Escherichia coli O127:B8 was added at 100 ng / mL for 24 hours at 37° C, 5% CO2. Cell supernatants were collected, TNFa in cell supernatants was assayed by ELISA. As shown in Figure 12, the composition inhibits LPS- induced TNF-a release and therefore exhibits anti-inflammatory effects.The effect of the synthetic peptides of SEQUENCE ID NO. 28 and 29 on the IL-17A / IL- 23 / TH17 signalling axis was assessed using the QUANTI-Blue™ primary screening assay. The results are illustrated in Figure 13 and 14.ATP ProductionC2C12 cells were treated with a composition of the invention (5 to 50pg / ml) and analysed for metabolic changes using a SeaHorse analyser. Following a 20-minute stimulation with the composition, a significant increase in ATP production split evenly between glycolysis and oxidative phosphorylation was observed in murine C2C12 myoblasts (Figure 15). Increased glucose uptake into the muscle cell increases catabolic processes and subsequent ATP production via both glycolysis and oxidate phosphorylation. This suggests that in addition to its effects on vasodilation via ACEi, the composition may also support aspects of muscle performance and energy.EquivalentsThe foregoing description details presently preferred embodiments of the present invention. Numerous modifications and variations in practice thereof are expected to occur to those skilled in the art upon consideration of these descriptions. Those modifications and variations are intended to be encompassed within the claims appended hereto.

Claims

Claims1 . A peptide up to 50 amino acids in length, comprising an amino acid sequence selected from SEQUENCE ID NO. 22, SEQUENCE ID NO. 1 to 21 , and SEQUENCE ID NO. 23 to 30, or an effective variant of the amino acid sequence.

2. The peptide of Claim 1 , wherein the variant comprises 1 to 3 amino acid changes compared with the sequence and wherein the or each amino acid change is independently selected from a deletion, addition, substitution and insertion.

3. The peptide of Claim 1 or 2, wherein the peptide has ACE inhibitory activity.

4. The peptide of any one of the preceding claims, wherein the peptide is modified, preferably to increase the stability of the peptide.

5. The peptide of any one of the preceding claims, wherein the peptide comprises an amino acid sequence selected from SEQUENCE ID NO. 31 to 366.

6. A conjugate comprising one or more peptide of any one of Claims 1 to 5, conjugated, linked or fused to a binding partner.

7. A composition comprising one or more peptides of any one of Claims 1 to 5 or the conjugate of Claim 6.

8. A composition of Claim 7, comprising a peptide comprising SEQUENCE ID NO. 22, or an effective variant thereof.

9. The composition of Claim 7, comprising one or more peptides selected from the group comprising, a peptide comprising SEQUENCE ID NO. 15, a peptide comprising SEQUENCE ID NO. 16, a peptide comprising SEQUENCE ID NO. 17, a peptide comprising SEQUENCE ID NO. 18, a peptide comprising SEQUENCE ID NO. 19, a peptide comprising SEQUENCE ID NO. 20, a peptide comprising SEQUENCE ID NO. 21 , a peptide comprising SEQUENCE ID NO. 22, a peptide comprising SEQUENCE ID NO. 23, a peptide comprising SEQUENCE ID NO. 13, a peptide comprising SEQUENCE ID NO. 24, a peptide comprising SEQUENCE ID NO. 25, a peptide comprising SEQUENCE ID NO. 3, a peptide comprising SEQUENCE ID NO. 26, a peptide comprising SEQUENCE ID NO. 27, a peptide comprising SEQUENCE ID NO. 28, a peptide comprising SEQUENCE ID NO. 29 and a peptide comprising SEQUENCE ID NO. 30, or variants thereof.

10. The composition of Claim 8, comprising, a peptide comprising a peptide comprising SEQUENCE ID NO. 15, a peptide comprising SEQUENCE ID NO. 16, a peptide comprising SEQUENCE ID NO. 17, a peptide comprising SEQUENCE ID NO. 18, a peptide comprising SEQUENCE ID NO. 19, a peptide comprising SEQUENCE ID NO. 20, a peptide comprising SEQUENCE ID NO. 21 , a peptide comprising SEQUENCE ID NO. 22, a peptide comprising SEQUENCE ID NO. 23, a peptide comprising SEQUENCE ID NO. 13, a peptide comprising SEQUENCE ID NO. 24, a peptide comprising SEQUENCE ID NO. 25, a peptide comprising SEQUENCE ID NO. 3, a peptide comprising SEQUENCE ID NO. 26, a peptide comprising SEQUENCE ID NO. 27, a peptide comprising SEQUENCE ID NO. 28, a peptide comprising SEQUENCE ID NO. 29 and a peptide comprising SEQUENCE ID NO. 30.11 . The composition of Claim 8, comprising one or more peptides selected from the group comprising, a peptide consisting of SEQUENCE ID NO. 15, a peptide consisting of SEQUENCE ID NO. 16, a peptide consisting of SEQUENCE ID NO. 17, a peptide consisting of SEQUENCE ID NO. 18, a peptide consisting of SEQUENCE ID NO. 19, a peptide consisting of SEQUENCE ID NO. 20, a peptide consisting of SEQUENCE ID NO. 21 , a peptide consisting of SEQUENCE ID NO. 22, a peptide consisting of SEQUENCE ID NO. 23, a peptide consisting of SEQUENCE ID NO. 13, a peptide consisting of SEQUENCE ID NO. 24, a peptide consisting of SEQUENCE ID NO. 25, a peptide consisting of SEQUENCE ID NO. 3, a peptide consisting of SEQUENCE ID NO. 26, a peptide consisting of SEQUENCE ID NO. 27, a peptide consisting of SEQUENCE ID NO. 28, a peptide consisting of SEQUENCE ID NO. 29 and a peptide consisting of SEQUENCE ID NO. 30.

12. The composition of any one of Claims 7 to 11 , which is a powder.

13. A nutritional or dietary supplement comprising a peptide of any one of Claims 1 to 5, a conjugate of Claim 6, or a composition of any one of Claims 7 to 12.

14. A peptide of any one of Claims 1 to 5, a conjugate of Claim 6, a composition of any one of Claims 7 to 12 or a supplement of Claim 13, for use in treating or preventing hypertension in a subject.

15. A non-therapeutic method to improve sexual function in a subject, the method comprising administering a peptide of any one of Claims 1 to 5, a conjugate of Claim6, a composition of any one of Claims 7 to 12 or a supplement of Claim 13, to said subject.

16. A peptide of any one of Claims 1 to 5, a conjugate of Claim 6, a composition of any one of Claims 7 to 12 ora supplement of Claim 13, for improving or maintaining muscle status in a subject.

17. A non-therapeutic method for enhancing physical performance in a subject, the method comprising administering a peptide of any one of Claims 1 to 5, a conjugate of Claim 6, a composition of any one of Claims 7 to 12 or a supplement of Claim 13, to said subject.

18. The non-therapeutic method of Claim 16, for enhancing physical performance during exercise.

19. A non-therapeutic method for reducing post exercise fatigue in a subject, the method comprising administering a peptide of any one of Claims 1 to 5, a conjugate of Claim 6, a composition of any one of Claims 7 to 12 or a supplement of Claim 13, to said subject.

20. A peptide of any one of Claims 1 to 5, a conjugate of Claim 6, a composition of any one of Claims 7 to 12 or a supplement of Claim 13, for use in reducing inflammation in a subject.

21. A peptide of any one of Claims 1 to 5, a conjugate of Claim 6, a composition of any one of Claims 7 to 12 or a supplement of Claim 13, for use in preventing or treating an inflammatory disorder in a subject.

22. A non-therapeutic method for increasing energy in a subject, the method comprising administering a peptide of any one of Claims 1 to 5, a conjugate of Claim 6, a composition of any one of Claims 7 to 12 or a supplement of Claim 13, to said subject.

23. A peptide of any one of Claims 1 to 5, a conjugate of Claim 6, a composition of any one of Claims 7 to 12 or a supplement of Claim 13, for use in preventing or treating post-infection fatigue.

4. A peptide of any one of Claims 1 to 5, a conjugate of Claim 5, a composition of any one of Claims 6 to 11 or a supplement of Claim 12, for use in treating or preventing early hypertension in a subject, wherein the subject is at risk of developing hypertension.

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