Peptides

<p>Amyloid β-peptide (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.</p>

<p>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. Synthetic 3CLpro substrates are being generated for their potential to inhibit the protease activity and thus replication cycle of coronaviruses.When this peptide is intact, fluorescence from the fluorophore (donor) EDAN is undetectable due to the proximity of the acceptor (quencher) Dabcyl. However, upon cleavage the fluorescence of the EDANS moiety, as measurably by excitation/emission 340/490nm, can be detected due to separation from the Dabcyl quencher. This product was shown to be a potent inhibitor of 3CLpro activity therefore, it has the potential to be a vital tool in the fight against SARS-CoV.</p>

<p>Amino acids 1-10 of human adrenocorticotropic hormone (ACTH). ACTH, also known as corticotropin, is a tropic hormone produced and secreted by the anterior pituitary gland and member of the melanocortins peptide family. ACTH is cleaved from the precursor proopiomelanocortin (POMC). ACTH is an important component of the hypothalamic-pituitary-adrenal (HPA) axis and is often produced in response to biological stress. ACTH acts to increase the production and release of cortisol via its interaction with the ACTH receptor- ACTHR, also known as melanocortin type 2 receptor (MC2R). Receptor activation increases the intracellular concentration of cAMP via adenylyl cyclase.Abnormal ACTH levels in the body has been linked to primary adrenal insufficiency/Addison's disease, Cushing's disease and secondary adrenal insufficiency.</p>

<p>Triptorelin is an agonist of gonadotrophin-releasing hormone (GnRH-R). Androgen-deprivation therapy (ADT), based on GnRH agonists and antagonists, is the standard therapeutic approach for prostate cancer (PCa) patients. In castration-resistant prostate cancer (CRPC) GnRH agonists are associated with significant anti-proliferative/pro-apoptotic, anti-metastatic and anti-angiogenic effects, mediated by the Gαi/cAMP signalling cascade. The tryptophan residue in this peptide is replaced with the D-amino acids making the peptide resistant to degradation from proteases and therefore increasing the half-life of the peptide in vivo. Peptide is for research purposes only, strictly not for human use.</p>

<p>Derived from fibronectin, integrin-binding cell adhesive peptide can be used as an adhesion ligand, it contains the cell binding motif RGD. Providing integrin-mediated cell adhesion is a valuable tool for a wide variety of research applications particularly in cell culture and implants. The integrin-binding cell adhesive peptide can also functionalise biomolecules. This has been successfully demonstrated by the generation of a protease-degradable hydrogel containing the integrin-binding cell adhesive peptide that can support skin formation in vitro. Integrin-binding cell adhesive peptide has also been used to form hydrogels to adhere numerous cell lines, for example to study extracellular vesicle secretion.</p>

<p>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 SWFTALTQHGKEDLK (51-65) 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.</p>

<p>Galanin is a widely distributed neuropeptide in the central nervous system, peripheral regions and endocrine system. Galanin has a role in energy homeostasis. Central injections of galanin to the amygdala led to food intake in rats. Galanin also acts in the CNS to inhibit neurotransmitter release, such as acetylcholine. Galanin has been implicated in numerous neurological conditions, including Alzheimer's disease, depression, and epilepsy.Galanin interacts with 3 receptor subtypes, GalR1-3 G protein-coupled receptors which are inserted into the plasma membrane. GalR1 is believed to activate a Gβγ pathway to regulate MAPK activation. GalR2 can also activate the MAPK pathway, but unlike GalR1, there is detectable inositol phosphate production. GalR3 is associated with the Galphai/o pathway- receptor activation leads to a cellular influx of potassium ions.The galanin active fragment (1-16) has been identified as a highly potent agonist for the galanin receptors from binding assays.  This has become a basis for galanin-based peptides, which are neuroactive. These are being investigated as a potential source for anticonvulsant neuropeptides as a therapeutic for conditions such as epilepsy. A library of galanin fragments has allowed screening of their properties to be assessed and used to generate chimeric peptides. Galanin fragments have different affinities for GalR receptors- however, the N-terminal (1-16) residues have been shown to have a conserved affinity for the receptors. This galanin (2-13) peptide is provided in the amide form. The acidic form is also available in our catalogue.</p>

<p>SARS-CoV-2 NSP7 is part of the RNA-dependent RNA polymerase heterotetramer for mediating coronavirus RNA synthesis. NSP7 and NSP8 form a channel to confer processivity on RNA polymerase. NSP7 aids in stabilising NSP12 regions involved in RNA binding and is essential for a highly active NSP12 polymerase complex. These factors make NSP7 a good target for developing new antiviral drugs. In addition, the identification of epitopes within the NSP7 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. NSP7 (31-45) 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.</p>

<p>DOTA-conjugated somatostatin analogue for labelling with radiometals such as gallium-67 or gallium-68, indium-111, and yttrium-90. Known as DOTA-TATE, this is a useful tool in receptor-mediated tumour imaging and peptide receptor-targeted radionuclide therapy. Binding of DOTA-TATE is detected by scintigraphy even at low level. The high expression of somatostatin receptors allows their successful use as radiolabelled octreotide analogues for tumour tracing in nuclear medicine. Binding of DOTA-TATE can occur at sights of inflammatory or immunologic diseases where increased lymphocyte binding is occurring.A few radioligands have been applied on the basis of peptide receptor recognition in the past. However, an optimal radiopeptide for receptor-targeted radionuclide therapy has yet to be achieved. Ongoing developments may result in peptides more suitable for this kind of receptor-targeted radionuclide therapy. Further work with this DOTA-TATE could provide that vital inroad.</p>

<p>Peptide corresponding to residues 206-214 of murine islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP), the autoantigen targeted by pathogenic CD8+ T cells in non obese diabetic (NOD) mice. Cells that recognize IGRP(206-214) are present in the earliest islet infiltrates of NOD mice and undergo avidity maturation as islet inflammation progresses to overt disease.</p>

<p>Alloferon 1, a member of the Alloferons is extracted from the blood of experimentally infected Callifora vicina fly and demonstrates both antimicrobial and anti-tumour activity . The Alloferons are bioactive, cationic peptides and exhibit the ability to stimulate Natural Killer cell activity and IFN synthesis. Due to studies investigating the effect Alloferon 1 would have on the central nervous system it was shown that Alloferon 1 had no toxic effects and therefore has the potential to be used as an anti-tumour therapeutic.</p>

Fluorogenic substrate peptide of the 20S proteasome. In its intact state this peptide is non-fluorescent, however when Rhodamine fluorophore is released upon hydrolysation, fluorescence can be detected. This peptide is therefore a useful tool for analysing the activity of the 20S proteasome as well as other chymotrypsin-like proteases and calpains. This peptide is also a substrate for chymase, papain, carboxypeptidase Y, proteinase yscE (kexin) and ingensin.The presence of the D-proline residue on the C terminal of the rhodamine molecule ensures one directional rhodamine cleavage which simplifies fluorescence studies. Rhodamine 110 is a laser grade fluorescent dye with excitation maxima at 496 nm and emission maxima at 522 nm.

<p>Palmitoyl GQPR tetrapeptide.</p>

<p>Biotin-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 Biotin-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, Biotin-TAT (47-57) can be used to deliver proteins, fluorophores, chelators and DNA to target cells.This peptide contains a covalently bonded N-terminal Biotin tag that can be used for detection and purification.</p>

<p>Protease activated receptors (PARs) are a distinctive four-member family of seven transmembrane G protein-coupled receptors (GPCRs) widely expressed in inflammatory cells. PARs are cleaved by certain serine proteases to expose a tethered ligand domain, this ligand domain then binds to and activates the receptors to initiate multiple signalling cascades. These PAR-activating proteases therefore represent PAR agonists. This PAR-2 agonist peptide mimics the sequence of the 'tethered ligand' and is therefore capable of activating the receptor independently of N-terminal proteolysis.SLIGRL-NH2 inhibits the development of airway eosinophilia, hyper-responsiveness and displays bronchodilator activity in allergic mice and also facilitates gastrointestinal transit in mice-in vivo.PAR activation has been linked to inflammation, therefore compounds that mimic or interfere with the PAR-activating processes are attractive therapeutic candidates.</p>

<p>SARS-CoV-2 NSP13 (336-350)</p>

<p>H-STMSIT-OH peptide, corresponding to RNase A 77-82 (Chain A of bovine pancreatic ribonuclease) has been published to have amyloidogenic properties, and under certain conditions H-STMSIT-OH hexapeptide forms amyloid fibrils. Please also see CRB1001321, which you can use as a negative control in amyloid formation experiments.</p>

<p>Myocarditis is an inflammatory heart disease often associated with a previous viral infection. Evidence has suggested that myocarditis may be due to autoimmune responses directed against cardiac tissue. The inflammatory immune response caused after infection may break tolerance by mechanisms of molecular mimicry, bystander activation, and loss of immune regulation. Experimental autoimmune myocarditis (EAM) is a model of inflammatory heart disease generated by immunizing susceptible rats or mice with cardiac myosin or its myocarditic epitopes. In the EAM model, cellular infiltrates consist primarily of T cells and macrophages, and T lymphocytes responsive to cardiac myosin can transfer disease. Cardiac myosin is a large peptide, which is composed of two H chains and two pairs of L chains. Proteolysis of myosin yields three subfragments including a globular head or subfragment 1 (S1) region, an alpha helical coiled coil rod comprised of subfragment 2 (S2), and light meromyosin (LMM). In the Lewis rat, the S2 subfragment has been shown to produce the most severe myocarditis.</p>

<p>The gp91 ds-TAT peptide is composed of a gp91phox sequence conjugated to the human immunodeficiency virus-TAT peptide. The TAT sequence facilitates its entry into all cells, hence it is a cell-penetrating peptide. The gp91 peptide is the haem binding sub-unit of the superoxide-generating NADPH oxidase. As a result, the gp91 ds-TAT peptide can be used as a selective inhibitor of NADPH oxidase assembly.Recent studies have shown that gp91 ds-TAT can increase blood nitric oxide bioavailability in hind limb ischaemia and reperfusion by inhibiting NADPH oxidase.</p>

<p>PMX 53 is a potent antagonist of CD88, a G protein-coupled receptor for C5a (complement protein). C5a is a protein fragment released from cleavage of complement component C5 by protease C5-convertase into C5a and C5b fragments. C5a, the other cleavage product of C5, acts as a highly inflammatory peptide, encouraging complement activation, formation of the MAC, attraction of innate immune cells, and histamine release involved in allergic responses. The origin of C5 is in the hepatocyte, but its synthesis can also be found in macrophages, where it may cause local increase of C5a. C5a is a chemotactic agent and an anaphylatoxin- it is essential in the innate immunity but it is also linked with the adaptive immunity. The increased production of C5a is connected with a number of inflammatory diseases.By antagonising the C5a receptor, PMX can be used to modulate inflammatory responses, obesity, development and cancers.</p>

<p>Histone 3 (H3) 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. 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. 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.The lysine at position 4 of this peptide has been tri-methylated and it is implicated in studies that this modification may remodel the chromatin so that it is more accessible to transcription factors, which may ultimately increase the level of gene expression. Moreover, the serine at position 10 has been phosphorylated, and studies have suggested that this may induce chromatin condensation, and subsequently repress transcription and gene expression.Histone H3 (1-20) K4Me3, pS10-GG-[Lys(5-FAM)] has a C-terminal GKK linker labelled with 5-Carboxyfluorescein (5-FAM), a widely used green fluorescent tag.</p>

<p>ACTH is a member of the melanocortins peptide family, this tropic hormone is produced and secreted by the anterior pituitary gland. ACTH is an important component of the hypothalamic-pituitary-adrenal (HPA) axis and is often produced in response to biological stress. ACTH acts to increase the production and release of cortisol via its interaction with ACTHR. Receptor activation increases the intracellular concentration of cAMP via adenylyl cyclase. Abnormal ACTH levels in the body have been linked to primary adrenal insufficiency/Addison's disease, Cushing's disease and secondary adrenal insufficiency.It contains 5-Carboxyfluorescein (5-FAM), a widely used green fluorescent tag.</p>

<p>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 LIDLQELGKY (1197-1206) 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.</p>

<p>Arginine vasopressin (AVP) is a neurohypophysial hormone that is synthesized in the supraoptic nucleus and paraventricular nucleus of the hypothalamus. The major function of AVP is to regulate extracellular fluid volume and electrolyte homeostasis via its anti-diuretic action. It is also a vasoconstrictor and pressor agent. AVP is important to the central nervous system (CNS) and also has physiological actions in the peripheral organs, such as the kidney, heart and vascular beds.</p>

<p>Human γHV Epstein-Barr virus (EBV) is host-specific, making it challenging to study. Evidence suggests EBV infection provides an enhanced immune response against other future heterologous infections. Murid herpesvirus 4 (MuHV-4) in mice can be used as a model to help understand herpesviruses. The peptide provided here (ORF65131-140) has been used in CTL assays to show that MuHV-4 improves the effector CD8+ T cells response against a heterologous virus. MuHV-4 ORF65131-140 epitope can stimulate interleukin production ex vivo and be detected by tetramer staining to MHC. Further work with MuHV-4 ORF65131-140 could be crucial for understanding the reactivity of the human immune system to other viruses after infection with γHV Epstein-Barr virus (EBV).</p>

<p>This peptide is recognised and cleaved by the enzyme Sortase A (SrtA) from-Staphylococcus aureus. The catalytic cysteine residue in the active site of SrtA, serves as a nucleophile to cleave the peptide bond between threonine and glycine. Cleavage results in the formation of a thioacyl intermediate between the peptide and SrtA. This intermediate is then resolved by the N-terminus of an (oligo)glycine nucleophile, resulting in the creation of a new peptide bond that links the peptide and its biotin tag to the incoming nucleophile.- This method of protein labelling is known as sortagging.This peptide contains an N-terminal biotin tag for detection and purification.</p>

<p>Galanin (1-30) (human) is an endogenous neuropeptide with endocrine, metabolic and behavioural effects. Galanin has a role in intestinal smooth muscle contraction, insulin and somatostatin release, and synaptic neurotransmission.Galanin is widely distributed in the central nervous, peripheral, and endocrine systems. Galanin's overarching function is as an inhibitory, hyper-polarizing neuromodulator for classical neurotransmitters like acetylcholine and serotonin. Galanin interacts with 3 receptor subtypes, GalR1-3 G protein-coupled receptors inserted into the plasma membrane. GalR1 is believed to activate a Gβγ pathway to regulate MAPK activation. GalR2 can also activate the MAPK pathway, but unlike GalR1, there is detectable inositol phosphate production. GalR3 is associated with the Galphai/o pathway. Activation of the receptor leads to a cellular influx of K+. Each receptor has been associated with neurological diseases such as GalR3 and epilepsy.Galanin protects against various physiological insults in vitro, including excitotoxicity and β-amyloid toxicity. Changes in galanin have been widely studied concerning Alzheimer's disease, and galaninergic neurons are spared in late-stage Alzheimer's relative to non-galaninergic neurones.Galanin (1-30) has been used as an agonist for the GalR2 receptor in vitro for calcium mobilisation assays to understand the role Galanin/GalR2 play in multiple sclerosis.Galanin (1-30) is provided with an N-terminal 5-TAMRA, a widely used red fluorescent reagent ideal for peptide labelling and detection. The excitation/emission for this reagent is 555 nm/580 nm.</p>

The RGD peptide is a ligand for cell-surface integrin receptors, which are used by most cells to attach to and sense the extracellular environment and to establish a cytoskeleton. RGD peptide can be attached to biologically important molecules, such as nanoparticles, to enable active targeting of drugs or gene delivery. Model substrates presenting immobilised RGD peptide can be used to promote the adhesion and spreading of cells which have been engineered to expresses integrin receptors such as the platelet cell-surface integrin receptor, alphaIIbβ3. Cells growing in these conditions appear to have well developed cytoskeletons suggesting that binding to the integrin receptor mediates biologically relevant adhesion and RGD substrates are able to support cell survival. Peptide is labelled with an N-terminal 5-carboxyfluorescein (5-FAM), a widely used green fluorescent tag.

<p>This 19 amino acid fragment of myelin basic protein (MBP) can induce experimental allergic encephalomyelitis (EAE) in Lewis rats. EAE is the most commonly used experimental model for studying the human inflammatory demyelinating disease, multiple sclerosis (MS).MBP is an integral component of myelin found in the central nervous system (CNS). MBP is considered vital for the development and stability of the myelin sheath where it plays a role in membrane adhesion. MPBs constitute an extraordinarily varied collection of splice isoforms which show a myriad of post-translational modifications. MBP may be targeted by auto-antibodies in diseases such as multiple sclerosis. The low affinity of MBP (1-9) peptide for MCH class II molecules may result in MBP autoreactive T cells escaping central-tolerance, where self-reactive T cells are usually eliminated.</p>

<p>This peptide is recognised and cleaved by the enzyme Sortase A (SrtA) from-Staphylococcus aureus. The catalytic cysteine residue in the active site of SrtA, serves as a nucleophile to cleave the peptide bond between threonine and glycine. Cleavage results in the formation of a thioacyl intermediate between the peptide and SrtA. This intermediate is then resolved by the N-terminus of an (oligo)glycine nucleophile, resulting in the creation of a new peptide bond that links the peptide and its biotin tag to the incoming nucleophile.- This method of protein labelling is known as sortagging.This peptide contains an C-terminal biotin tag for detection and purification.</p>

<p>SPA4 is a surfactant protein-A (SP-A)-derived peptide which is an antagonist of toll-like receptor-4 (TLR4). SP-A and TLR4 have been identified as important pathogen-pattern recognition receptors (PPRRs). SP-A represents the majority of SPs and plays a key role in fighting pathogens and down-regulating inflammation, whereas TLR4 recognises pathogens and endogenous stress proteins and induces the inflammatory and adaptive immune responses.Over-activation of TLR4 induces inflammatory response via NF-KB and TNF-α cytokine. SPA4 has been shown to bind to TLR4 and inhibit the release of TNF-α in response to the most potent TLR4-ligand: Gram-negative bacteria-derived lipopolysaccharide (LPS), however SPA4 does not interfere with LPS binding to TLR4. The suppression of LPS-TLR4 signalling by SPA4 peptide alleviates inflammatory response.</p>

<p>Fluorescently labelled 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 which has the sequence AVLQSGFRK. SARS-CoV Mpro is a key antiviral target.This peptide contains a highly fluorescent N-terminal 7-methoxycoumarin fluorophore (Mca) and a 2,4-dinitrophenyl (Dnp) quencher. Mca is efficiently quenched by resonance energy transfer to the 2,4-dinitrophenyl group when the peptide is intact, however upon cleavage of the peptide by Mpro, the Mca group and the Dnp quencher are separated and fluorescence can be detected. This therefore represents a useful tool for investigating Mpro activity.</p>

<p>An angiotensin II (Ang-II) receptor antagonist, the sequence of the angiotensin II anti-peptide has been derived from the anti-sense mRNA complementary to the human Ang-II mRNA. The anti-peptide shares 50% sequence homology with Ang-II and acts to inhibit some of Ang-II's biological activities.Ang-II is a key signalling peptide of the renin angiotensin system (RAS), which is involved in regulating blood pressure, cardiovascular function and energy balance. RAS activity is elevated in obesity and is widely studied in relation to lifestyle-related diseases. Ang-II is produced from angiotensinogen (AGT) via the intermediate angiotensin I (Ang-I). AGTis cleaved by the aspartyl-protease, renin, to produce Ang-I, which is then cleaved by the dicarboxyl-peptidase angiotensin converting enzyme (ACE). ACE removes a histidine and a leucine, from the C-terminus of Ang-I to form Ang-II.Ang-II exerts its affect by binding to the G-protein-coupled receptors- Ang II type 1 (AT1) and Ang II type 2 (AT2) receptors. Ang-II plays central roles in glucose metabolism and blood pressure. Increased levels of Ang-II have also been associated with Alzheimer's disease, and certain cancers including oesophageal squamous cell carcinoma (ESCC), brain cancers and breast cancer. The effects of Ang-II appear to be supressed by another branch of the RAS- the ACE2/Ang-(1-7)/Mas pathway.</p>

<p>Palmitoyl KTTKS pentapeptide.</p>

<p>There are three members of the p160 family of steroid receptor coactivators, SRC-1, SRC-2, and SRC-3. These steroid receptor coactivators control the functional output of numerous genetic programs and serve as pleiotropic rheostats for diverse physiological processes. Coactivator proteins interact with nuclear receptors in a ligand-dependent manner and augment transcription.</p>

<p>Cell penetrating peptides (CPP) are a useful tool for drug delivery, but their cell-specific uptake is still being improved. Work with the model amphipathic peptide (MAP) has been important in this field. CPP MAP is an amphipathic α-helix and has been well characterised for its ability to spontaneously permeate the cell membrane by interacting with the lipid bilayer. As a CPP, MAP causes increased membrane permeability and a degree of cell leakage. MAP is being extensively studied to optimise drug delivery in numerous cell lines with the target of creating a viable clinical method. Interestingly, the CPP function of MAP also provides it with bactericidal properties by effecting the membrane permeability. MAP is a potent antimicrobial peptide (AMP) against gram negative Neisseria meningitidis, the pathogen of meningococcal disease.MAP 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-MAP allows a wide variety of applications particularly for conjugation, modification, and peptide design.</p>

<p>Histatins are histidine rich cationic peptides produced in salivary glands and released into the saliva. The main histatins that make up more than 80% of histatins in saliva are histatin 1, histatin 3 and histatin 5. There are two histatin genes, one which encodes histatin 1, and one that encodes histatin 3, all other histatins are derivatives of these two histatins. Histatin 3 is a precursor of histatin 5, each with distinct roles.Histatin 5  is considered an antimicrobial peptide (AMP) as it has antibacterial activity as has been shown against opportunist infections such as P. aeruginosa, E. coli, and S. aureus. Histatin 5 also has potent anticandidal activity for example against Candida and Leishmania, it is shown to be the strongest antifungal of the histatins.  The antifungal activity functions by invasion of the microbe and entry to the mitochondria, histatin 5 then inhibits ATPase activity resulting in rapid depletion and ultimately bacterial cell death/apoptosis. As a salivary peptide, it inhibits Bacteroides gingivalis proteinase clostripain and protease activity microbe implicated in periodontal disease.</p>

<p>This is an incretin hormone that causes glucose dependent release of insulin by pancreatic beta cells. It is the cleavage product of GLP-1 (1-36) amide peptide.  This peptide, human GLP-1 (7–36), shares the same sequence with preproglucagon (78-107), amide, human.</p>

<p>HLA-A*02 is a class I major histocompatibility complex (MHC) allele which is part of the HLA-A group of human major histocompatibility complex (MHC) leukocyte antigens (HLA), found at the HLA-A locus. HLA-A is one of three major types of human MHC class I cell surface receptors. The receptor is a heterodimer, and is composed of a heavy alpha chain and smaller β chain. MHC Class I molecules such as HLA-A are part of a process that presents short polypeptides to the immune system. These polypeptides are typically 7-11 amino acids in length and originate from proteins being expressed by the cell. Cytotoxic T cells in the blood "read" the peptide presented by the complex and should only bind to non-self peptides. If binding occurs, a series of events is initiated culminating in cell death via apoptosis. This peptide corresponds to the Hepatitis B variant (HBV) core sequence which is presented on the MHC class I antigen HLA-A*02 and contains fluorescein, a widely used flourescent dye.</p>

<p>EB1 is a penetratin analogue that was synthesised to be an endosomolytic cell penetrating peptide (CPP). Certain amino acids in the penetratin sequence were replaced with histidine to encourage formation of an alpha helix upon protonation in the acidic endosomes. As a CPP, EB1 has been shown to form a strong interaction with the phospholipid bilayer during insertion with rapid cellular uptake, there is a moderate amount of cell leakage and no significant cytotoxicity. EB1 is provided here as a C-terminal amide with a N-terminal 5-carboxyfluorescein (5-FAM), a widely used green fluorescent tag often preferred due to its high stability absorbance 492 (nm), 518 emission (nm).</p>

<p>AAT is a highly abundant serine protease inhibitor primarily produced in the liver to protect the lung tissue. However, misfolding of AAT can result in significant liver disease, lung disease, and cancers. Defective AAT is characteristic of the misfolding protein diseases known as serpinopathies.Ion mobility mass spectrometry (IM-MS) was used to identify Ac-TTAI-amide as a ligand effecting α1-antitrypsin stability. Interaction of Ac-TTAI-amide with AAT results in increased stability and reduced polymerisation. Thus Ac-TTAI-amide is a useful target for further research in to serpinopathy management.</p>

<p>The AH1 peptide is a H2-Ld-restricted epitope derived from the sequence of the gp70 envelope protein of the ecotropic mammalian C-type retrovirus, murine leukaemia virus (MuLV, emv-1).The envelope gene products of MuLV are expressed in a variety of tumour cells, including B16 melanoma, lymphomas and leukaemia's. AH1 peptide is a tumour-associated antigen and is highly expressed on CT26 and C51 tumour cells.</p>

<p>A20FMDV2, a peptide derived from the foot and mouth disease virus, inhibits the epithelial-specific integrin alphavβ6 and here is labelled with 4-fluorobenzoyl as the light version of the PET ligand 4-[18F]Fluorobenzoyl A20FMDV2 which can be used for in vivo imaging.</p>

<p>Amino acids 1-15 of β-amyloid protein (Aβ), this fragment represents one of many short Aβ species found in vivo and is formed by the cleavage of amyloid β precursor protein by β- and α-secretase.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.</p>

<p>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.</p>

Fluorogenic substrate peptide of the 20S proteasome. In its intact state this peptide is non-fluorescent, however when aminomethylcoumarin (AMC) is released upon hydrolysation, fluorescence can be detected. This peptide is therefore a useful tool for analysing the activity of the 20S proteasome as well as other chymotrypsin-like proteases and calpains. This peptide is also a substrate for chymase, papain, carboxypeptidase Y, proteinase yscE (kexin) and ingensin.AMC is a fluorescent dye with excitation maxima at around 360 nm and emission maxima at around 450 nm. AMC can be excited with a mercury lamp and observed using a UV filter set.

<p>Venom peptidomes and proteomes have yielded significant novel drug discoveries. The non-disulphide bridge peptides (NDBPs) have become a particular focus due to their large range of structures as well as biological activity while retaining high specificity.In scorpion venom A. crassicauda, AcrAP1 was identified as a NDBP. Data shows it has antimicrobial activity against bacteria and yeast while also capable of haemolysing of horse erythrocytes. However, AcrAP1 did not affect the growth of the cancerous cell lines tested. Therefore, this peptide could be a useful model for modification to improve its potency. Furthermore, it may allow researchers to identify specific targets in disease pathways for new drug designs. A significant example of this, bradykinin-potentiating peptide Captopril® manages hypertension and originated from the conserved NDBP family.</p>

<p>The pathology of cardiovascular disease (CVD) is linked to the health of endothelial cells in the heart.- However, the specific characteristics of the cardiovascular endothelial cells are still being uncovered. The heart homing peptide specifically binds to a receptor on cardiovascular endothelial cells. This peptide can be used as a conjugate to deliver molecules specifically to the heart. This can be a crucial tool in therapeutic drug delivery for CVD, angiogenesis, and thrombosis.</p>

<p>α-connexin carboxyl terminal peptide that specifically targets and maintains Cx43 at gap junction sites between cell-cell membrane borders of breast cancer cell.- Thus it augments gap junction activity and impairs proliferation and survival of breast cancer cells with no effect on non-transformed cells.</p>

<p>Histone H3 (1-20) K4Me3-GG-[Lys(5-FAM)] 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.The lysine at position 4 of this peptide has been tri-methylated and it is implicated in studies that this modification may remodel the chromatin so that it is more accessible to transcription factors, which may ultimately increase the level of gene expression.Additionally, Histone H3 (1-20) K4Me3-GG-[Lys(5-FAM)] has a C-terminal GKK linker labelled with 5-Carboxyfluorescein (5-FAM), a widely used green fluorescent tag. This peptide also has an uncharged C-terminal amide.</p>