Peptides

TAT-TRPV1 (736-745) is a cell-permeable TRPV1 fragment (capsaicin receptor and the vanilloid receptor 1), that can inhibit the interaction of TRPV1 and A-kinase anchoring protein 79 (AKAP79). TAT- TRPV1 (736-745) consists of amino acids 736-749 from the TRPV1 C-terminal domain, combined with amino acids 47-57 of TAT to promote uptake across neuronal cell membranes. TAT-TRPV1 (736-745) inhibits both the first and the second phase of pain behaviour in the formalin test, implying an effect on both acute and inflammatory pain.A-kinase anchoring protein 79 (AKAP79) is a protein that targets kinases to TRPV1. Inflammation causes hyperalgesia but can be reduced when TRPV1 is blocked. a key region on AKAP79, amino acids 326-336, is responsible for its interaction with TRPV1. TAT-TRPV1 (736-745) promotes uptake across the cell membrane and TRPV1 (736-745)  inhibited inflammatory hyperalgesia in mice. TAT-TRPV1 (736-745) did not affect pain thresholds in the absence of inflammation. These results suggest that antagonizing the TRPV1-AKAP79 interaction will be a useful strategy for inhibiting inflammatory hyperalgesia and TAT is an effective delivery system.

Magainins, also known as PGS (peptide glycine serine) are anti-microbial peptides originally isolated from the skin of the African clawed frog Xenopus laevis, they belong to a large family of amphibian amphipathic alpha-helical cationic anti-microbial peptides (CAMPs). Magainin II is active against a wide spectrum of pathogens including Gram-positive and Gram-negative bacteria, fungi and protozoa and has anti-viral properties. Magainins also displays anti-tumour activities and are known to facilitate wound closure and to reduce inflammation.Magainin peptides act by first binding to and then causing eventual collapse of the membrane. Magainins, carry several positive charges, and interact best with membranes with a negative surface charge, such as bacteria or tumour cells. They are non-toxic to healthy eukaryotic cells which are charge-neutral at their outer membrane. The physical mode of action of these peptides reduces the ability of target organisms to develop resistance to them, suggesting good therapeutic potential.

ANP (human) is derived from the atrial natriuretic peptide (ANP) which is a cardiac hormone involved in maintaining cardio-renal homeostasis. This occurs through the activation of the guanylyl cyclase-coupled receptor, resulting in the increased concentration of cyclic guanylate monophosphate. Moreover its function in the processes of anti-proliferation and anti-angiogenesis allow it to take part in cardiovascular remodelling.ANP is a member of the natriuretic peptide family and it is encoded by the NPPA gene, located on chromosome 1. Once synthesized from the 151 amino acid pre-prohormone into its biologically active form, ANP is secreted by the atrial cardiomyocytes in the circulating forms: ANP (1-98) and ANP (99-126). This synthesis process involves the signal peptide being removed from the pre-prohormone resulting in pro-ANP (1-126) which is converted into the circulating forms by the type II transmembrane serine protease Corin.At the N-terminus Azhx, 6-azidohexanoic acid, is present.

protein transduction domain PTD-5 is a cell-penetrating peptide (CPP). PTD-5 is well characterised for its ability to carry conjugates into the cell with high efficiency and induce low toxicity. Several papers have demonstrated the efficacy of PTD-5 as a CPP- PTD-5 was also conjugated to KLA to produce a pro-apoptotic peptide named DP1 which is selective for mitochondrial and bacterial membranes.PTD-5 is labelled at the N-terminus with an alkyne attachment for ease of reaction with an opposite Click reactive partner (azide). Azide-alkyne cycloaddition has become the most popular Click reaction. Alkyne-PTD-5 allows various applications, particularly for protein conjugation, modification, and drug delivery.

Polybia-MPI is a short cationic alpha-helical amphiphilic anti-microbial peptide which was first isolated from the venom of the social wasp Polybia paulista. Polybia-MPI displays potent anti-bacterial activity against both Gram-positive and Gram-negative bacteria and is able to disrupt biofilms. Polybia-MPI also has anti-fungal activity against C. albicans and C. galbrata and selective toxicity toward cancer cells. Polybia-MPI has low toxicity to normal fibroblasts and human red blood cells, showing no haemolytic activity.

Jelleines are a family of very small (8-9 amino acid residues long) host defence peptides (HDPs) isolated from the royal jelly of honey bees (Apis mellifera). Jelleines do not present any similarity with other HDPs from other honeybees and are produced by the workers and secreted into Royal Jelly and provide abroad-spectrum protection of the bee hive against microbial infections. The Jelleines are not considered cytolytic or directly involved with inflammatory effects.PLEASE NOTE that in several published articles the sequence of Jelleine-3 has been printed as TPFKISLH -NH2, due to a mistake in the original reference: Fontana et al., (2004). The correct sequence, is TPFKISIH -NH2.

Portion of EBV RTA

GGG-C(AF647) C-Terminal Sortagging

Histone H3 (1 - 20) K4Me3 is derived from Histone 3 (H3), which is one of the four core histones (H2A, H2B, H3 and H4) fundamental in compacting eukaryotic DNA into the nucleosome. The nucleosome arises when 147 base pairs of DNA wrap around a H3-H4 tetramer and two H2A-H2B dimers, forming the histone octamer core. H4 and H3 are highly conserved and perform roles in binding to segments of DNA which enter and leave the nucleosome and in chromatin formation. Like the other core histone, H3 has a globular domain and a flexible N-terminal domain, 'histone tail' which can undergo modifications such as acetylation, methylation, phosphorylation and ubiquitination. Due to histones containing many lysine and arginine residues, they have a positive net charge which interacts electrostatically with the negatively charged phosphate groups in DNA. The transcriptional activation or silencing of the chromatin is controlled by ATP-dependent chromatin remodelling factors and histone-modifying enzymes which target histone proteins. Both processes alter the positioning of the nucleosome, allowing the DNA to be either available or inaccessible to the transcription machinery.Histone tails can undergo multiple modifications, including acetylation, methylation, ubiquitylation and sumoylation.  The modification pattern is believed to alter chromatin function/structure.  Lysine 4 of histone H3 (1 - 20) K4Me3 has been tri-methylated, lysine 9 has been acetylated, and serine 10 has been phosphorylated and labelled with Biotin. This peptide can be used to study the function of this pattern on chromatin availability and histone effectors via crystallisation, pull-down assays and protein blots.

The SARS-CoV-2 spike protein is present on the outside of the virus particles and can bind to angiotensin-converting enzyme II (ACE2) present on the host cells. The C-terminal receptor binding domain (RBD) of the spike protein binds to the N-terminal peptidase M2 domain of ACE2. This receptor binding results in the internalisation of the virus-receptor complex and is, therefore the mechanism of entry of SARS-CoV-2 into host cells.The spike protein residues VFAQVKQIYKTPPIK (781-795) from C have been identified as a T-cell epitope with a predicted HLA restriction. Immune targeting of confirmed epitopes may potentially offer protection against SARS-CoV-2 and help the development of vaccines for long-lasting immunity.

Histone H3 (1-22) is derived from Histone 3 (H3) which is one of the four core histones (H2A, H2B, H3 and H4) fundamental in compacting eukaryotic DNA into a structure known as the nucleosome. The nucleosome arises when 147 base pairs of DNA wrap around a H3-H4 tetramer and two H2A-H2B dimers, forming the histone octamer core. Both H4 and H3 are highly conserved and perform roles in binding to segments of DNA which enter and leave the nucleosome and in chromatin formation. Similar to the other core histone, H3 has a globular domain and a flexible N-terminal domain 'histone tail' which can undergo modifications such as acetylation, methylation, phosphorylation and ubiquitination. Due to histones containing a large number of lysine and arginine residues they have a positive net charge which interacts in an electrostatic manner with the negatively charged phosphate groups in DNA. The transcriptional activation or silencing of the chromatin is controlled by ATP-dependent chromatin remodelling factors and histone modifying enzymes which target histone proteins. Both processes function to alter the positioning of the nucleosome, allowing the DNA it to be either available or inaccessible to the transcription machinery.

Portion of HCMV

LL-13-37 is an active fragment of the LL-37 peptide which has been shown to have anti-fungal properties against Candida albicans.LL-37 is a member of the large cationic family of anti-microbial peptides called cathelicidins which have broad-spectrum anti-microbial activity and are expressed in many species. The only cathelicidin found in humans is LL-37- this is produced in epithelial cells, by proteolytic cleavage from the C-terminal of the hCAP-18 protein. LL-37 can be processed into different forms of anti-microbial peptides. As well as its anti-microbial properties LL-37 also has anti-cancer properties and regulates many aspects of the innate immune system- overexpression of LL-37 has been linked to autoimmune diseases such as asthma and psoriasis.

Portion of EBV BMLF1

The coronavirus (CoV) nucleoprotein is the major component of CoV structural proteins. The nucleoprotein has a critical role in virus assembly and RNA transcription. The nucleoprotein is essential in the formation of helical ribonucleoproteins and in regulating viral RNA synthesis. The nucleoprotein can also regulate infected host cellular mechanisms. It is highly expressed during infection and may induce protective immune responses against SARS-CoV and SARS-CoV-2.The nucleoprotein residues KEDLKFPRGQGVPIN (61-75) from SARS-CoV-2 have been identified as a T-cell epitope with a predicted HLA restriction. Immune targeting of confirmed epitopes may potentially offer protection against SARS-CoV-2 and help the development of vaccines for long-lasting immunity.

Gastric inhibitory polypeptide (GIP) is an inhibiting hormone of the secretin family of hormones. While GIP is a weak inhibitor of gastric acid secretion, its main role is to stimulate insulin secretion - in a glucose-dependent mechanism. Therefore, GIP is referred to as a glucose-dependent insulinotropic peptide. In GIP (Pro 3) the glutamic acid at position 3 has been substituted for a proline.GIP is derived from a 153-amino acid proprotein encoded by the GIP gene and circulates as a biologically active 42-amino acid peptide. It is synthesised by K cells, which are found in the mucosa of the duodenum and the jejunum of the gastrointestinal tract. GIP receptors are seven-transmembrane proteins found on β-cells in the pancreas. These β-cells are those that are able to simultaneously detect glucose and release insulin as a result to GIP binding.The clinical relevance of GIP is related to type 2 diabetes mellitus (T2DM)- studies have found that T2DM diabetics are unresponsive to GIP and have lower levels of GIP secretion after a meal when compared to non-diabetics. In research involving knockout mice, it was found that absence of the GIP receptors correlates with resistance to obesity.

N-terminal biotin adrenocorticotropic hormone (ACTH). ACTH, also known as corticotropin, is a cleavage product from a larger precursor proopiomelanocortin (POMC). This 39 amino acid-peptide hormone is produced in the anterior pituitary gland upon stimulation by the corticotropin releasing hormone from the hypothalamus in response to stress. It stimulates the secretion of steroid hormone, specifically glucocorticoids in the adrenal cortex by acting through a cell membrane receptor (ACTH-R). In mammals, the action of ACTH is limited to those areas of the adrenal cortex in which the glucocorticoid hormones cortisol (hydrocortisone) and corticosterone are formed. ACTH has little control over the secretion of aldosterone, the other major steroid hormone from the adrenal cortex.

SGS-acid is a tripeptide consisting of a serine residue followed by a glycine and another serine residue. SGS-acid was synthesised from the dipeptide glycyl-L-serine (GS-acid)- the dipeptide GS-acid is also available in our catalogue. SGS-acid has a net charge of 0, it can act as a Bronsted base by accepting a hydron from a donor thus giving it diverse biological and chemical uses.

Aβ has been identified as the key subunit of the extracellular plaques found in the brains of patients with Alzheimer disease (AD) and Down syndrome (DS). Aβ has therefore been extensively studied as a potential target for treatment of AD.Aβ is formed from the cleavage of the large, transmembrane protein- APP (amyloid precursor protein). Cleavage of APP by β- and then &γ--secretases results in the formation of Aβ. Aβ can aggregate to produce amyloid-β oligomers, which are thought to be highly neurotoxic. Over time Aβ can further aggregate to produce the characteristic senile plaques present in AD and DS. Aβ can be degraded by enzymes such as neprilysin, insulin degrading enzyme or endothelin converting enzyme. At physiological levels Aβ may be involved in controlling synaptic activity and neuronal survival.

Numerous studies have found BMAP-28 to have AMP activity against various bacteria, fungi, and some parasites such as Leishmania. Of note, studies show it inhibits multi-drug resistant (pan-resistant) species of both Gram-negative and Gram-positive bacteria including Acinetobacter baumanniim, Pasteurella multocida, and MRSA. With the rise in antibiotic-resistant species, BMAP-28 is a useful discovery for creating new more potent analogues.In mammalian studies BMAP-28 induces cancer cell death and prevents growth, via inducing mitochondrial pore opening and depolarisation leading to cell apoptosis making it a target for future cancer treatment.

Herceptide

Substrate for the severe acute respiratory syndrome coronavirus main protease (SARS-CoV Mpro). The substrate sequence is derived from residues P4-P5' of the SARS-CoV Mpro N-terminal autoprocessing site and was identified by a docking study. This substrate binds to and acts as a competitive inhibitor of SARS-CoV Mpro, (3CLpro).Experiments show that the octapeptide AVLQSGFR is bound to SARS-CoV Mpro through six hydrogen bonds. It is an effective inhibitor of SARS coronavirus with an EC50 of 2.7 x 10-2 mg/L and is able to block replication of the virus. The octapeptide also shows no detectable toxicity in the host cells.

Glucagon like-peptide-2 (GLP-2) is a gut hormone produced in the enteroendocrine L cells of gastrointestinal tract by the cleavage of the 160-amino-acid proglucagon molecule. GLP-2 is secreted following the ingestion of food and carries out its activities via the GLP-2 G-protein coupled receptors (GLP-2Rs). GLP-2 has a range of roles within the cell, including: anti-inflammatory effects promoting the expansion of the intestinal mucosa, stimulating intestinal blood flow, inhibiting gastric acid secretion and gastric emptying, increasing intestinal barrier function and enhancing nutrient and fluid absorption.

Pep-1 is a synthetic cell-penetrating peptide (CPP), and has been successfully used to deliver a variety of proteins and other biopharmaceutical macromolecules into cells in a non-disruptive manner. It is a CPP with primary amphipathicity, which results from its amino acid sequence as opposed to its folding structure. The primary structure of Pep-1: Chariot comprises three main domains: a tryptophan-rich, hydrophobic domain, and a hydrophilic domain derived from an NLS (nuclear localisation signal) of SV40 (simian virus 40) large T-antigen, and a spacer.

Fibrinogen (377-395) Human is derived from Fibrinogen, which is a large plasma glycoprotein with a complex structure, and one of the most abundant proteins in blood. Fibrinogen is important in fibrin clot formation, haemostasis, and inflammatory responses. Increased plasma fibrinogen indicates a proinflammatory state and is a risk factor for vascular inflammatory diseases including hypertension and atherosclerosis. Fibrinogen cleavage products act as inflammatory activators in the pathophysiology of allergic asthma.Fibrinogen (377-395) Human is capable of preventing microglia activation by inhibiting the Mac-1 receptor, which in turn suppresses relapsing paralysis.

TP10 is an amphipathic cell-penetrating peptide (CPPs) also known as transportan 10. Its formation involves the use of a lysine residue to form a chimeric linkage between a mastoparan 21-residue peptide, a wasp venon 14-residue peptide and 6-residues derived from the neuropeptide galanin. Structurally TP10 contains only positively charged amino acids along with 4 lysines and an N-terminus. Therefore it will produce a +5 charge under conditions of a neutral pH. It has been found that TP10 may aid molecules in penetrating through the cell membrane barrier through directly interacting with the lipid bilayer. During these interactions with the membrane TP10 will form an amphipathic alpha-helix. TP10 can be used in transduction methods.

HPV16 E6 pep11**m.

Amyloid β 1-15 (Aβ1-15) is one of many short Aβ species found in vivo and is formed by the cleavage of amyloid β precursor protein by β- and alpha-secretase.Aβ has been identified as the key subunit of the extracellular plaques found in the brains of patients with Alzheimer's disease (AD) and Down's syndrome (DS). Aβ has therefore been extensively studied as a potential target for treatment of AD.Aβ is formed from the cleavage of the large, transmembrane protein- APP (amyloid precursor protein). Cleavage of APP by β- and then γ-secretases results in the formation of Aβ. Aβ can aggregate to produce amyloid-β oligomers, which are thought to be highly neurotoxic. Over time Aβ can further aggregate to produce the characteristic senile plaques present in AD and DS. Aβ can be degraded by enzymes such as neprilysin, insulin degrading enzyme or endothelin converting enzyme. At physiological levels Aβ may be involved in controlling synaptic activity and neuronal survival.Contains an N-terminal Carboxytetramethylrhodamine (TAMRA) fluorophore. TAMRA is a pH-stable orange-red fluorescenct dye with good photostability.

VP4 is a viral coat protein of Nora virus encoded for by ORF4. The product of this gene is likely cleaved into three capsid proteins, VP4A, B and C. VP4 is also the most conserved gene from Nora virus and related viruses. Nora virus is a non-pathogenic virus found in gut of Drosophila melanogaster. It causes persistent, non-pathological infection, it replicates in the fly gut and is transmitted via the faecal-oral route. Nora virus has a 12333 nucleotides long single-stranded RNA genome of positive polarity.

The Histone H3 (22-30)-K27Me3 is derived from Histone 3 (H3) which is one of the four core histones (H2A, H2B, H3 and H4) fundamental in compacting eukaryotic DNA into the nucleosome. The nucleosome arises when 147 base pairs of DNA wrap around a H3-H4 tetramer and two H2A-H2B dimers, forming the histone octamer core. Both H4 and H3 are highly conserved and perform roles in binding to segments of DNA which enter and leave the nucleosome and in chromatin formation. Similar to the other core histone, H3 has a globular domain and a flexible N-terminal domain, 'histone tail' which can undergo modifications such as acetylation, methylation, phosphorylation and ubiquitination. Due to histones containing a large number of lysine and arginine residues they have a positive net charge which interacts in an electrostatic manner with the negatively charged phosphate groups in DNA. The transcriptional activation or silencing of the chromatin is controlled by ATP-dependent chromatin remodelling factors and histone modifying enzymes which target histone proteins. Both processes function to alter to change the positioning of the nucleosome, allowing the DNA it to be either available to the transcription machinery or inaccessible.The Histone H3 (20-36) lysine 27 has been trimethylated which is usually a marker of repressive chromatin. H3K27 trimethylation also prevents H3 from interacting with SET1-like complexes, thus inhibiting the trimethylation of H3K4.

The SARS-CoV-2 spike protein is present on the outside of the virus particles and can bind to angiotensin-converting enzyme II (ACE2) present on the host cells. The C-terminal receptor binding domain (RBD) of the spike protein binds to the N-terminal peptidase M2 domain of ACE2. This receptor binding results in the internalisation of the virus-receptor complex and is, therefore the mechanism of entry of SARS-CoV-2 into host cells.The spike protein residues VQIDRLITGR (991-1000) from SARS-CoV-2 have been identified as a T-cell epitope with a predicted HLA restriction. Immune targeting of confirmed epitopes may potentially offer protection against SARS-CoV-2 and help the development of vaccines for long-lasting immunity.

This insulin B-chain peptide binds to a class II histocompatibility complex (MHC) allele called I-Ag7. A number of autoimmune diseases has been linked to class II proteins encoded by the MHC. Type 1 diabetes, or insulin-dependent diabetes mellitus, is a T cell-mediated disease that results in autoimmune destruction of pancreatic ß cells leading to hyperglycemia. This insulin β peptide may be a self-antigen candidate that could initiate the disease. Immunisation with this peptide in mice led to autoantibodies and insulitis. In the non-obese diabetic (NOD) mouse model, this peptide represents the dominant insulin peptide driving disease initiation.Insulin is a polypeptide composed of two peptide chains referred to as the alpha chain and β chain. Insulin is normally secreted rapidly from the β-cells of the pancreatic islets in response to nutrients absorbed after a meal. In type 1 diabetes mellitus, there may be an absolute insulin deficiency as a consequence of autoimmune destruction of the β-cells.

Forms of inherited muscular dystrophy such as Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) result from mutations targeting the dystrophin gene. These disorders are X-linked, progressive, and cause the gradual weakening of the muscles leading to respiratory failure and ultimately reduces the patient lifespan.In DMD, mutations lead to the production of premature stop codons and hence the truncated dystrophin protein product is vulnerable to nonsense mediated decay and degradation. Therefore, dystrophin production in muscle cells is reduced. On the other hand, nonsense mutations which also contribute to DMD, cause exon skipping in BMD and result in an internally truncated protein product which are partially functional. The symptoms of BMD are later onset compared with DMD which develop in patients between 2 to 7 years.Treatments of dystrophin disorders are in clinical trials including antisense oligonucleotide exon skipping and gene therapy. However, the efficacies of these treatments are not easily quantified. Currently levels of muscular dystrophin are quantified by western blot which can be unreliable. The peptide provided here, aligning residues dystrophin (50-61), has been used to try and create a quantifiable method that is reproducible. The method used was not successful, but dystrophin (50-61) remains a useful tool to create a potential quantification method for diagnosis and progress of dystrophin disorders as it was effectively detected by mass spectrometry and Western blot. Within our catalogue we also have other peptides tested for dystrophin quantification available plus the full-length dystrophin protein.

The coronavirus (CoV) nucleoprotein is the major component of CoV structural proteins. The nucleoprotein has a critical role in virus assembly and RNA transcription. The nucleoprotein is essential in the formation of helical ribonucleoproteins and in regulating viral RNA synthesis. The nucleoprotein can also regulate infected host cellular mechanisms. It is highly expressed during infection and may induce protective immune responses against SARS-CoV and SARS-CoV-2.The nucleoprotein residues FKDQVILLNKHIDAY (346-360) from SARS-CoV-2 have been identified as a T-cell epitope with a predicted HLA restriction. Immune targeting of confirmed epitopes may potentially offer protection against SARS-CoV-2 and help the development of vaccines for long-lasting immunity.

Insulin is a polypeptide composed of two peptide chains referred to as the alpha chain and β chain. These chains are linked by two disulphide bonds, and an additional disulphide is formed within the alpha chain. In most species, the alpha chain consists of 21 amino acids and the β chain of 30 amino acids. Insulin is normally secreted rapidly from the β-cells of the pancreatic islets in response to nutrients absorbed after a meal. In type 1 diabetes mellitus, there may be an absolute insulin deficiency as a consequence of autoimmune destruction of the β-cells. On the other hand, in type 2 diabetes mellitus, insulin secretion is impaired and is inadequate to overcome peripheral insulin resistance.

C5a receptor peptide antagonist which can ameliorate experimentally-induced colon inflammation in mice. It can also reduce fibrillar amyloid deposits, decrease hyperphosphorylated tau levels and rescue cognitive function in a mouse model of Alzheimer's Disease. Also improves hindlimb grip strength and slows disease progression in the hSOD1G93A-mouse model of amyotrophic lateral sclerosis. Orally active and brain penetrant.

Tetanus Toxin P2 (830 - 844) is a protein that is derived from the single-chain polypeptide neurotoxin produced by Clostridium tetani. The neurotoxins produced by Clostridium tetani are among the most potent molecules known to humankind. Once in the body, the toxin binds to the basal lamina at the neuromuscular junction. From here, the toxin is transported to inhibitory interneurons in the spinal cord, where it prevents the release of neurotransmitters, which causes spastic paralysis.The P2 protein has antigenic properties that are reflective of the neurotoxin released by Clostridium tetani. Therefore, P2 is a suitable epitopes for CD4+ T cells and can be used to stimulate the release of IFNg, which is a cytokine that promotes macrophage activity and coordinates lymphocyte endothelium interactions.

[5-FAM]-TAT (47-57) is a cell penetrating cationic peptide derived from the N-terminus of the Tat protein, which is a trans-activator of the transcription protein present in the human immunodeficiency virus (HIV). Specifically TAT (47-57) is located within the arginine-rich basic domain 48-60 of the TAT peptide which as a whole has three domains which function to aid HIV through transactivation, DNA binding and nuclear transport. As a cell penetrating peptide (CPP) TAT aids in the cellular uptake of molecules and hence serves a valuable purpose in transduction methods. This property has been demonstrated through its ability of allowing toxins such as the neurotoxin Botulinum neurotoxin Type A, produced by the Clostridium botulinum type A bacteria to penetrate the skin barrier non-invasively. Additionally TAT (47-57) can be used to deliver proteins, fluorophores, chelators and DNA to target cells.It contains 5-carboxyfluorescein (5-FAM), a widely used green fluorescent tag.

Ganglioside GM1-binding peptides p3.

This peptide constitutes the acetylated N-terminal region of murine myelin basic protein (MBP) and displays high affinity for major histocompatibility complexes (MHC). This high MHC affinity is due to substitution of the native lysine at position 4 for a tyrosine. Substitution increases the MHC binding affinity of the peptide by around 1 million fold, therefore creating a superagonist ligand. MBP is an integral component of myelin found in the central nervous system (CNS) vital for the development and stability of the myelin sheath where it plays a role in membrane adhesion. MBP may be targeted by auto-antibodies in diseases such as multiple sclerosis. The low affinity of the native lysine containing MBP 1-9 peptide for MCH class II may result in MBP auto-reactive T cells escaping central-tolerance where self reactive T cells are usually eliminated. MBPs constitute an extraordinarily varied collection of splice isoforms which show a myriad of post-translational modifications.

The coronavirus (CoV) nucleoprotein is the major component of CoV structural proteins. Also known as the nucleocapsid protein, it is an abundant RNA-binding protein critical for viral genome packaging. These factors make nucleoprotein a good target for developing new antiviral drugs. In addition, the identification of epitopes within the nucleoprotein sequence can help design more effective SARS-CoV-2 vaccines.Models have predicted epitopes exhibiting antigenicity, stability and interactions with MHC class-I and class-II molecules. Nucleoprotein (261-275) is an epitope candidate with various HLA restrictions. This epitope can be used to better vaccine design for more durable CD4+ and CD8+ T cell responses for long-lasting immunity.

Steroid Receptor Coactivator - 1 (676-700).

Pathogenic Staphylococcus aureus strains produce N-formylmethionyl containing peptides. Peptides starting with an N-formylated methionyl group constitute a unique hallmark of bacterial as well as mitochondrial metabolism, and professional phagocytes of our innate immune system recognise this microbial/mitochondrial pattern as a danger signal that guides innate immune cells.All PSMα peptides have the same basic functions and promote virulence through effects on discrete neutrophil functions (i.e. chemotaxis) and by being cytotoxic at higher concentrations. PSMα2 and PSMα3 can both bind to FPR2 and trigger superoxide release in neutrophils at low nanomolar concentrations. In addition, at high nanomolar concentrations they display cytotoxicity selectively on apoptotic neutrophil membranes and this occurs in an FPR2 independent manner.

The full Rev is vital in aiding transport of unspliced viral mRNA from the nucleus. Within Rev there are 3 main functional regions - the arginine rich motif (ARM), the oligomerization domain (OD), and nuclear export sequence (NES). The peptide sequence 34-50 aligns to the ARM motif which binds the Rev Response Element (RRE) in RNA to form a complex which ultimately leads to nuclear export. ARM is able to recognise a wide range of RNA sequence to and still bind to form a Rev dimer. The Rev ARM sequence has also been shown to work as a nuclear localisation sequence that can penetrate cells. In research, Rev ARM has been utilised as a cell penetrating peptide (CPP) for its ability to bind RNA due to the arginine residues presenting multiple sides for binding and thus deliver macromolecules into the cell.

Venom peptidomes and proteomes have the potential for significant inroads to novel drug discovery. The non-disulphide bridge peptides (NDBPs) have become a particular focus due to their large range of apparent structures and biological activity while retaining high specificity. Additionally, it has been found that a few site-specific modifications or post-translational modifications can have significant impacts on the potency of their biological effects.Within the peptidome AcrAP1 was identified in the NDBP as having antimicrobial and bactericidal activity. The nascent peptide contains a predicted hydrophobic region, this was altered to lysine residues generating a hydrophilic region, AcrAP1a. This cationic enhancement markedly increases their antibacterial potency against bacteria and yeast. Furthermore, at relatively high concentrations, it inhibited proliferation of several cancer cell lines but at low concentrations in 2 cell lines the growth was significantly promoted. The duality of AcrAP1a on growth modulation in cancer cell lines as well as having potent antimicrobial activity suggests it is a useful analogue for further research in bacteria and eukaryotes.

Panx-1 mimetic inhibitory peptide that blocks pannexin-1 gap junctions. Inhibits P2X7-mediated dye uptake, ATP-mediated IL-1β release and caspase-1 activation without altering membrane current in macrophages. It can also block activation of NMDA receptor secondary currents.

CMV pp65 (415-429) (HLA-B7) is a CEF (cytomegalovirus, Epstein-Barr virus, and influenza virus) control peptide that is derived from the Cytomegalovirus (CMV). CMV is capable of infecting a wide range of human cell types, where the body's primary immune response to CMV is innate, and relies on inflammatory cytokines and costimulatory molecules in order to control the spread of the virus. CMV pp65 (415-429) (HLA-B7) is defined as a CEF control peptide due to its antigenic properties. Clinically, these peptides are suitable epitopes for CD8+ T cells and can be used to stimulate the release of IFNg. HLA-B7 refers to the cell HLA type that this peptide acts on.

The biologically active C-terminal region of human Kisspeptin. Kisspeptin, is cleaved from a 145 amino acid precursor to a 54 amino acid peptide in humans and a 52 amino acid peptide in mice. Smaller isoforms of 14, 13 and 10 amino acids have also been isolated, each sharing the common C-terminal sequence. Kisspeptin-10 (KP-10) is the most potent member of the kisspeptin family and the plasma half-life of is approximately 6 fold shorter than KP-54. KP-10 is produced by the trophoblast cells in the first trimester of pregnancy and inhibits cell migration primary trophoblasts which is essential for placental invasion.Kisspeptin, a product of the KISS1 gene, is a hypothalamic neuropeptide that stimulates gonadotropin-releasing hormone (GNRH) neurons and drives fertility. Kisspeptin binds specifically to the G-protein-coupled receptor-54, now known as Kiss1r, which is expressed in almost all GNRH neurons. Kiss1r is also expressed in other areas of the brain and periphery, highlighting other possible roles for kisspeptin outside of reproduction.

3CLpro are the key enzymes required by coronaviruses to replicate. They cleave polyproteins to form replicase. This makes 3CLpro a drug target for protease inhibitors with particular interest to COVID-19. For, example Paxlovid®- has been brought to market as a 3CLpro inhibitor that can be administered orally to reduce coronavirus disease 19 (COVID-19) hospitalisation. Aiming to expand on such advances, synthesis of more substrates for 3CLpro are being generated and tested for their ability to inhibit the protease activity and thus replication cycle of coronaviruses. This product is the natural substrate for 3CLpro, this makes it a useful tool as a control but also for structural manipulation to design inhibitors.

Histone H3 (1-18) is derived from Histone 3 (H3) which is one of the four core histones (H2A, H2B, H3 and H4) fundamental in compacting eukaryotic DNA into the nucleosome. The nucleosome arises when 147 base pairs of DNA wrap around a H3-H4 tetramer and two H2A-H2B dimers, forming the histone octamer core. Both H4 and H3 are highly conserved and perform roles in binding to segments of DNA which enter and leave the nucleosome and in chromatin formation. Similar to the other core histone, H3 has a globular domain and a flexible N-terminal domain 'histone tail' which can undergo modifications such as acetylation, methylation, phosphorylation and ubiquitination. Due to histones containing a large number of lysine and arginine residues they have a positive net charge which interacts in an electrostatic manner with the negatively charged phosphate groups in DNA. The transcriptional activation or silencing of the chromatin is controlled by ATP-dependent chromatin remodelling factors and histone modifying enzymes which target histone proteins. Both processes function to alter the positioning of the nucleosome, allowing the DNA it to be either available or inaccessible to the transcription machinery.

PDGF-Ra agonist with in vitro and in vivo antimelanoma growth activity.

[β-Ala]-[Lys(AMCA)]-acid.

Histone 4 (H4) is one of the four core histones (H2A, H2B, H3 and H4) which are fundamental in compacting eukaryotic DNA into the nucleosome. Due to the high lysine and arginine content, histones have a net positive charge and therefore electrostatically interact with negatively charged DNA. The nucleosome arises when 147 base pairs of DNA wrap around a H3-H4 tetramer and two H2A-H2B dimers, forming the histone octamer core. Like other core histones, H4 has a globular domain and a flexible N-terminal domain, the histone tail, which can undergo modifications such as acetylation, methylation, phosphorylation and ubiquitination.Gene transcriptional activation or inactivation is controlled by ATP-dependent chromatin remodelling factors and histone modifying enzymes. Both processes function to alter the positioning of the nucleosome, allowing the DNA within to be either accessible to the transcription machinery or inaccessible. H4's lysine rich tail plays a role in the higher order chromatin folding.

Histone H3 (10-29)-Biotin is derived from Histone 3 (H3) which is one of the four core histones (H2A, H2B, H3 and H4) fundamental in compacting eukaryotic DNA into the nucleosome. The nucleosome arises when 147 base pairs of DNA wrap around a H3-H4 tetramer and two H2A-H2B dimers, forming the histone octamer core. Both H4 and H3 are highly conserved and perform roles in binding to segments of DNA which enter and leave the nucleosome and in chromatin formation. Similar to the other core histone, H3 has a globular domain and a flexible N-terminal domain, 'histone tail' which can undergo modifications such as acetylation, methylation, phosphorylation and ubiquitination. Due to histones containing a large number of lysine and arginine residues they have a positive net charge which interacts in an electrostatic manner with the negatively charged phosphate groups in DNA. The transcriptional activation or silencing of the chromatin is controlled by ATP-dependent chromatin remodelling factors and histone modifying enzymes which target histone proteins. Both processes function to alter the positioning of the nucleosome, allowing the DNA it to be either available or inaccessible to the transcription machinery.Another modification process histones can undergo is biotinylation where the covalent attachment of a biotin molecule is catalysed by the enzyme Biotinidase. This cleaves biocytin to generate a biotinyl-thiester intermediate. The biotinyl can then be transferred onto the histone lysine ɛ-amino group which is covalently attached to Histone 3. Overall the biotinylation sites identified in histone 3 are: K4, K9 and K18. The presence of biotinylated histones have been detected in human cells such as lymphocytes and lymphomas.

Cell penetrating peptides (CPP) can transport molecules such as nucleic acids, proteins, and imaging agents into cells of interest. Pas PR9, nona-arginine, is an arginine rich CPP. It is composed of the nona-arginine: R9 and Pas which is a peptide penetrating accelerating sequence (PAS) and it functions to export molecules out of endocytic vesicles. During a study in which PR9 was in complex with a Quantum dot probe (QD) it was evident that the PR9/QD complex was transported into the cell through endocytosis and co-localises with actins, lysosomes, early endosomes and the nucleus. Due to the non-toxicity of the PR9/QD complex it can be used as a safe vector for biomedical purposes.PR9 is provided here with a N-terminal alkyne attachment. Two of the most regularly encountered functional groups for click chemistry are azides and alkynes, and the azide-alkyne cycloaddition has become the most popular click reaction. The use of click chemistry with alkyne- PR9 allows a wide variety of applications particularly for conjugation, modification, and peptide design.

Histone H3 (1-21) K4ac is derived from Histone 3 (H3) which is one of the four core histones (H2A, H2B, H3 and H4) fundamental in compacting eukaryotic DNA into the nucleosome. The nucleosome arises when 147 base pairs of DNA wrap around a H3-H4 tetramer and two H2A-H2B dimers, forming the histone octamer core. Both H4 and H3 are highly conserved and perform roles in binding to segments of DNA which enter and leave the nucleosome and in chromatin formation. Similar to the other core histone, H3 has a globular domain and a flexible N-terminal domain, 'histone tail' which can undergo modifications such as acetylation, methylation, phosphorylation and ubiquitination. Due to histones containing a large number of lysine and arginine residues they have a positive net charge which interacts in an electrostatic manner with the negatively charged phosphate groups in DNA. The transcriptional activation or silencing of the chromatin is controlled by ATP-dependent chromatin remodelling factors and histone modifying enzymes which target histone proteins. Both processes function to alter to change the positioning of the nucleosome, allowing the DNA it to be either available to the transcription machinery or inaccessible.The Histone H3 (1-21) lysine 4 has been acetylated.

Jelleines are a family of very small (8-9 amino acid residues long) host defence peptides (HDPs) isolated from the royal jelly of honey bees (Apis mellifera). Jelleines do not present any similarity with other HDPs from other honeybees and are produced by the workers and secreted into Royal Jelly and provide abroad-spectrum protection of the bee hive against microbial infections. The Jelleines are not considered cytolytic or directly involved with inflammatory effects.Possess antimicrobial properties against yeast, fungi, gram-positive and gram-negative bacteria.PLEASE NOTE that in several published articles the sequence of Jelleine-3 has been printed as EPFKISLHL-NH2, due to a mistake in the original reference: Fontana et al., (2004). The correct sequence, is EPFKISIHL-NH2.

GIP (1-30) Human amide is derived from the Gastric inhibitory peptide (GIP). Gastric inhibitory polypeptide (GIP) is an inhibiting hormone of the secretin family of hormones. While GIP is a weak inhibitor of gastric acid secretion, its main role is to stimulate insulin secretion - in a glucose-dependent mechanism. Therefore, GIP is referred to as a glucose-dependent insulinotropic peptide.GIP is derived from a 153-amino acid pro-protein encoded by the GIP gene. It is synthesised by K cells, which are found in the mucosa of the duodenum and the jejunum of the gastrointestinal tract. GIP receptors are seven-transmembrane proteins found on β-cells in the pancreas. These β-cells are those that are able to simultaneously detect glucose and release insulin as a result to GIP binding.The clinical relevance of GIP is related to type 2 diabetes mellitus (T2DM)- studies have found that T2DM diabetics are unresponsive to GIP and have lower levels of GIP secretion after a meal when compared to non-diabetics. In research involving knockout mice, it was found that absence of the GIP receptors correlates with resistance to obesity.

Pantinin-1 is an antimicrobial peptide (AMP) identified from the venom of the scorpion Pandinus imperator. Pantinin-1 possess strong antimicrobial activity against Gram-positive bacteria and fungus, and weak activity against Gram-negative bacteria, with very low haemolytic activities against human red blood cells.

Apoptosis can be triggered by permeabilization of the mitochondrial membrane leading to leakage of cytochrome c. Work shows this mitochondrial pathway to apoptosis involves pro-apoptotic proteins of the Bcl-2 family including Bak that directly permeabilise the mitochondrial membrane leading to leakage and catastrophic cell damage. The activities of apoptotic proteins are held in check by antiapoptotic paralogs, including Bcl-2. The interactions between these proteins are modulated by BH3-only proteins. BH3 proteins have 9 -15 amino acid BH3 domain and act as direct activators or sensitizers of pro-apoptotic proteins including Bak. PUMA has been identified as a BH3 protein, but its role is less clear. PUMA BH3 peptide provided here is the full 15 residue domain shown to act as a direct activator of Bak activity leading to caspase activity and apoptosis. A direct interaction with Bak has been demonstrated by surface plasmon resonance analysis. Critical data of PUMA and Bak regulation has not been well established. Further work with this peptide may help to clarify the function and role of the PUMA BH3 domain as a direct Bak activator.

Indolicidin is a natural cationic cathelicidin family anti-microbial peptide (AMP) with a very wide killing spectrum which includes: Gram-positive and Gram-negative bacteria, fungi, protozoa and HIV.  It is also an immune system modulator and an inhibitor of aminoglycoside antibiotic-resistance enzymes.Indolicidin contains 5 tryptophan residues (39% of peptide content)- the highest tryptophan proportion ever seen in a peptide or protein.When indolicidin interacts with biological membranes it assumes a wedge- shaped conformation, with the hydrophobic tryptophan residues in the trough of the wedge, and positively charged regions flanking them at each end. If fully extended, indolicidin is able to span both lipid bilayers despite only consisting of 13 amino acid residues. This is possible because indolicidin adopts an approximate poly-l-proline type II helix conformation, which is characterized by very high helical pitches.The exact mode of action of indolicidin is still unknown. At bactericidal concentrations the peptide appears to translocate through the membrane into the cytosol where it may bind to nucleic acids, whereas at higher concentrations it is membranolytic.

Peptide identified through phage display that binds to colorectal cancer cell line RKO cells, as well as other cancer cells including Caco-2, HCT 116 and HCT-15, but not to normal cells, possibly through targeting the monocarboxylate transporter 1, which has been implicated in colorectal cancer progression and prognosis.