Peptides

<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>

<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>

<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>IRBP (161-180) derived from the interphotoreceptor retinoid-binding protein (IRBP), present in the interphotoreceptor matrix and is expressed by cone and rod photoreceptors in the eye. IRBP is involved in retinoid delivery and protects retinal cells from oxidative stress.In retinitis pigmentosa patients, IRBP can be subjected to mutations resulting in a non-secreted form of IRBP to be produced. Furthermore IRBP gene mutations have been associated with high myopia and retinal dystrophy.The expression of IRBP is reduced in diabetes patients which may lead to visual cycle misfunction and the photoreceptors can be vulnerable to damage.</p>

<p>The SARS-CoV-2 non-structural protein 13 (NSP13) has been identified as a target for anti-viral therapeutics due to its highly conserved sequence and is essential for viral replication.  NSP13 is part of the helicase superfamily 1B. As an NTPase and RNA helicase, NSP13 binds to RNA-dependent RNA polymerase and acts in concert with the replication-transcription complex to stimulate backtracking and further activate NSP13 helicase activity. These factors make NSP13 a good target for developing new antiviral drugs. In addition, the identification of epitopes within the NSP13 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. NSP13 (466-480) is an epitope candidate with various predicted 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>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 biological activity while retaining high specificity.AcrAP2 was identified as a NDBP in A. crassicauda within highly conserved family of proteins. Data shows it has antimicrobial activity against bacteria and yeast while also capable of haemolysing horse erythrocytes. However, AcrAP2 did not affect the growth of 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>Sal-like4 (SALL4) derived peptide able to antagonise the SALL4-NuRD complex in hepatocellular carcinoma, turning SALL4 from a dual transcription repressor-activator to a singular transcription activator. Displays antitumour effects in xenograft mouse models.</p>

<p>TMPRSS4 (199-207) fluorogenic peptide</p>

<p>Small peptide design has become of interest to catalyse chemical transformations within the cell. The aim is to generate peptides to enhance the hybridization of attached oligonucleotides to complementary DNA sequences. (AAKK)4 is modelled on the surface of staphylococcal nuclease, it a short cationic lysine-rich peptide that can deliver a nucleophile to DNA or RNA. (AAKK)4 peptide can improve DNA-PNA (peptide nucleic acid) hybridisations dramatically as well as increase strand invasion rate. (AAKK)4 peptide is a non-lipid approach for cell penetration which is preferable for certain cell lines due to cytotoxicity issues. (AAKK)4-antisense conjugates have been used to silence gene expression.(AAKK)4 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-(AAKK)4 allows a wide variety of applications particularly for conjugation, modification, and peptide design.</p>

<p>SARS-CoV-2 NSP7 (1-15)</p>

<p>Bradykinins and their associated kinins are inflammatory mediators produced during inflammation. The two main kinins in mammals are the nonapeptide bradykinin, BK (1-9) and the decapeptide kallidin (KD), [Lys0]-BK(1-10). Their biological actions are mediated by two distinct receptors, termed B1 and B2.-BK is involved in several pathophysiological processes, such as inflammation, pain, cell proliferation, and tumours. It plays a crucial role in corneal epithelial cells, corneal stromal cells, and fibroblasts.Inflammation has been reported as one significant hallmark of breast cancer in relation to tumour development, metastasis, and invasion. The bradykinin receptor 1 (B1R) associated with kallidin is highly expressed on inflammatory breast tumour cells thus providing a promising targeting site for tumour recognition and sufficient receptor mediated endocytosis.</p>

<p>Histone H3 (1-21) K9Me2 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 9 has been dimethylated.</p>

<p>Peptide derived from the myosin heavy-chain (MyHC) proteins which are differentially expressed in mammalian skeletal muscles.</p>

<p>[5-FAM]-TAT 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.</p>

<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>The LDVP peptide (CS1), located in the type III connecting segment (V-region) of fibronectin, exhibits cell binding properties thus contributing to the adhesion of fibronectin to other cells.</p>

<p>Proinsulin connecting peptide (C-peptide), links the A and B chains of proinsulin. Upon enzymatic cleavage of C-peptide from pro-insulin in the pancreas, C-peptide is released into the blood stream along with insulin (A- and B-chains bonded together) in equimolar quantities. C-peptide can influence a wide variety of physiological conditions linked to diabetes, such as neuropathy, nephropathy, and encephalopathy. C-peptide is able to ameliorate and reverse the degrading effects of neuropathy in diabetes.</p>

<p>Acetylated α-synuclein (1-7) amide is derived from the alpha-synuclein intrinsically disordered protein which is found in the neurons and presynaptic terminals. Encoded by the SNCA1/PARK1 gene alpha-synclein is structurally composed of 140 amino acids, making up the three domains: N-terminal membrane binding domain, a hydrophobic non-amyloid-β component domain and a hydrophilic C-terminal domain. Usually alpha-synuclein plays a role in protecting neurons from apoptotic stimuli and is involved in synaptic vesical trafficking.However it has been found that the accumulation of alpha-synuclein aggregates can lead to neurodegenerative diseases such as Parkinson disease, dementia with Lewy bodies and multiple system atrophy. It is further involved in the fibrilisation of amyloid-b and tau which play a major role in Alzheimer disease. Amyloid fibrils are formed from alpha synuclein monomers within the cytosol and when bound to membranes these monomers can undergo conformational changes to form protofibrils and then ring like oligomers. This can result in the formation of transmembrane pores which disrupts the membrane, calcium homeostasis and signalling.Alpha-synuclein can be subjected to the post-translational modifications of phosphorylation and N-terminal acetylation. When acetylation occurs at the N-terminus of an alpha-synuclein monomer, the intramolecular hydrogen bonds are altered thus reducing the rate of alpha-synuclein aggregation and the strength at which it interacts with the membrane is increased.</p>

<p>Galanin is a widely distributed neuropeptide in the central nervous system (CNS), peripheral regions and endocrine system. Galanin interacts with 3 receptor subtypes, GalR1-3 G protein-coupled receptors inserted into the plasma membrane. 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. A better understanding of the galinergic signalling pathways may uncover a source for therapeutics for conditions such as epilepsy.Unlike human galanin, full-length porcine galanin contains only 29 amino acids and is C-terminally amidated. The first 15 residues are still highly conserved.  The best-recognized effect of galanin on the endocrine pancreas is the inhibition of insulin secretion in vitro and in vivo on multiple model systems, including rats, dogs, and mice. However, the same effect cannot be achieved at the same concentrations in human models with infusions of porcine galanin. Structural activity and point mutation studies show that the N-terminal (1-15) fragment is vital for the interaction/activation of the GAL receptor and the inhibition of insulin secretion.</p>

<p>Portion of EBV EBNA 3</p>

<p>[Nle12] alpha-factor is a cyclic analog of the Saccharomyces cerevisiae alpha-factor mating pheromone.</p>

<p>GQPR tetrapeptide.</p>

<p>Interactions between ECM proteins and growth factors were only thought to concentrate growth factors and to enhance their multimerisation for signalling. However, recent studies indicate that binding of growth factors to ECM proteins may enhance interactions between multi-domain ECM proteins, such as fibronectin (FN), with cell surface receptors, mostly integrins. The discovery of P12 revealed that a small peptide can mimic the role of FN with PDGF-BB, suggesting that some ECM-growth factor interactions may be less complex. P12 can not only bind to PDGF-BB, but also promote cell survival and improve rat skin burns in a dose dependent manner.P12 may have a clinical potential, especially in the reduction of cell death after tissue damage.</p>

<p>The MHC class II allele I-Ag7 is the allele associated with diabetes in the non-obese diabetic (NOD) mouse. I-Ag7 is also associated with spontaneous mouse models of arthritis and multiple sclerosis. The peptide mimotope mimics the structure of an epitope and therefore causes an antibody response similar to the one elicited by the epitope.</p>

<p>Antagonist peptide of VEGF-A and VEGF-B reproducing two binding regions of VEGF-B (loop 1 and loop3) linked together by a receptor binding region of VEGF-A (loop3). Binds to both VEGFR1 and VEGFR2 and inhibits VEGF-A driven proliferation, migration and tube formation in HUVECs.</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 GMEVTPSGTWLTYTG (321-335) 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>JAG-1(188-204). Jagged - 1 is a cell surface ligand for in the Notch pathway. Notch receptors and ligands are present on the extracellular service of cells and require cell-cell contact for engagement. Ligand binding to Notch receptors results in the proteolytic cleavage of membrane-bound Notch receptors, thus allowing the intercellular region to be transported to the nucleus and become a transcriptional activator. The ligand-induced Notch activation is regulated by E3 ubiquitin ligases, Mindbomb1 (Mib-1) and Neuralized.JAG1 is widely expressed throughout mammalian development, across many tissues and developmental stages. Notch signalling plays a critical role in cellular fate determination including muscle cell differentiation, neurogenesis, and the development of the sensory regions of the inner ear- heart- kidney- eye- lung and other tissues.Jag-1 has been implicated in breast- cervical- colorectal- endometrial- gastric- head and neck- ovarian- hepatocellular- lung- pancreatic- prostate, and kidney and adrenocortical cancers, leukemia and lymphoma. Co-overexpression of Notch-1 and Jagged-1 predicts the poorest overall cancer survival. JAG1 mutations have also been associated Alagille syndrome.</p>

<p>SARS-CoV-2 Nucleoprotein (331-345)</p>

<p>[5-FAM]-ERKtide</p>

This peptide is derived from gliadin wheat protein residues 31-43. It elicits an innate immune response by upregulating expression of interleukin (IL)-15 and cyclooxygenase (COX)-2. This peptide also promotes expression of CD25 on monocytes and macrophages, expression of CD83 on dendritic cells, and p38 MAP kinase activation. Treatment with this peptide allows immunodominant epitopes (57-68 and 62-75) to induce T-cell activation and enterocyte apoptosis.

<p>Reactivity to human leukocyte antigens (HLAs) is a rising concern in clinical treatments such as organ transplant rejection. Understanding the epitopes and the signalling pathways leading to reactivity could produce better clinical therapies in the future. The peptides presented by the non-classical HLA-G are important for a largely tolerogenic role and are considered part of an immune checkpoint. This, therefore, makes understanding ligand characteristics and HLA-G a target for cancer therapies. Interleukin-27 subunit β (22-30) fragment has been identified as an epitope that human leukocyte antigen HLA-G naturally presents, determined by liquid chromatographic tandem mass spectrometry (LC-MS/MS). This epitope has been used extensively in the literature to help understand the natural ligand presentation of HLA-G.For example, leukocyte immunoglobulin (Ig)-like receptors (LILRs) are key regulators of the immune response and therefore targets for therapeutics. Inhibitory LILRB1 and LILRB2 with HLA-G are pivotal for immunotolerance during pregnancy and autoimmune diseases plus cancer cell immune evasion. Interleukin-27 subunit β (22-30) fragment was used in binding affinity assays to clarify the conformational plasticity of the interaction between the receptor, the HLA antigen, and the various peptides HLA-G can accommodate.</p>

<p>AF12198 is a selective receptor antagonist to the human cytokine, type 1 interleukin-1 (IL-1) and thus blocks IL-1β signalling. AF12198 can inhibit IL-1-induced IL-8 production by human dermal fibroblasts and IL-1-induced intercellular adhesion molecule-1 (ICAM-1) expression by endothelial cells. AF12198 also blocks IL-1 induction of IL-6 and down regulates IL-6 induction in monkeys. AF12198 does not bind the human type II IL-1 receptor, or the murine type I IL-1 receptor.IL-1 influences a wide range of immune and inflammatory responses. Sustained expression of even low levels of IL-1 can be harmful in chronic inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease.</p>

<p>Represents the extracellular region of amyloid β peptide (Aβ). This region may be responsible for the conformational changes seen in Aβ and is cytotoxic in vitro.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 &amp;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>Eα antigen peptide, known to bind with high affinity to the major histocompatibility complex (MHC) class II molecule IAb. MHC class II molecules are normally found on antigen presenting cells such as dendritic cells, mononuclear phagocytes, endothelial cells, thymic epithelial cells and B cells and they present antigens derived from extracellular proteins. Eα peptide bound to IAb is specifically recognized by Y-Eα antibody.This peptide contains a C-terminal biotin tag for simple detection and purification.  The linker is ethylenediamine.</p>

<p>The progress of cardiovascular disease (CVD) comes from the damage and necrosis of cardiomyocytes. Although treatment has improved, once these cells are damaged, they cannot be recovered. Therefore, further research into cardiomyocytes is vital. Cardiomyocytes need to be in an exceedingly pure culture for research work. However, this requires identification of these cells from the ESCs present. With the use of a phage biopanning library, this sequence has been shown to have a high affinity to a receptor on the membrane surface of mouse ESC-derived cardiomyocytes. The functionality of this sequence allows it to be used a conjugate for drug or gene delivery to target cardiomyocytes or to purify cardiomyocytes in a research setting.</p>

<p>Peptide derived from vitronectin, the mammalian glycoprotein which plays a key role in tissue repair and remodelling. Its properties as an adhesive protein allow mammalian cells in serum to interact with culture vessels.</p>

<p>HIV-1 replication is rapid and error prone which is beneficial to the virus as it allows mutations to arise that aid evasion of the host immune system and resistance to drug treatment. RT is the key target for most anti-HIV drugs and therefore conserved sequences are useful to aid further research into new less toxic antiviral treatments.  HIV-1 reverse transcriptase (RT) converts the RNA genome into DNA during retroviral replication. HIV-1 RT is a heterodimer composed of 2 subunits, p66 and p51. HIV-1 RT heterodimer has 2 enzymatic functions, DNA polymerase and Rnase H resulting in nucleic acid translation to a linear DNA duplex. Complete inhibition of viral replication is the only known method of preventing HIV-1 drug resistance and disease progression.HIV RT epitopes have become a useful research tool as an in vitro antigenic challenge to study cytotoxic T lymphocyte (CTL) responses to retroviruses. The HIV-1 RT A2-YI9 sequence has been shown to be an effective epitope for CTL recognition leading to lysis of HIV-infected T cells. The A2-YI9 is also considered a potential for vaccine development due to it being a well conserved sequence. Synthesised HIV-1 RT A2-YI9 is provided here with N-terminal acetylation to mimic the charge of the native peptide more closely. The epitope is also available without acetylation from our catalogue.</p>

<p>Cyclic AC253 is an antagonist of the amylin receptor with neuroprotective effects against Aβ toxicity. Cyclic AC253 eliminates Aβ-induced impairment of hippocampal long-term potentiation and is able to penetrate the blood-brain barrier.</p>

<p>Identification of cell penetrating conjugates has aided numerous areas of scientific development. The Drosophila transcription factor Antennapedia contains a homeodomain that can be internalised by cells to the cytoplasm and to the nucleus in a receptor-independent mechanism. The key residues for internalisation have been sequenced (RQIKIWFQNRRMKWKK), named penetratin, and used in several studies to aid entry of fusion proteins into cells.The full 60 amino acid homeodomain was fused to a T cell epitope of the influenza nucleoprotein and successfully internalised into T cells for presentation. The CPP, penetratin, was fused to a ligand for Grb-2 resulting in inhibition of downstream Grb-2 signalling events.- Penetratin has also been used in vivo to prime cytotoxic T lymphocytes by conjugating short antigenic peptides to the CPP. Penetratin is provided here as a C-terminal acid but is also available in amide form.</p>

<p>(RXR)4XB is a cationic membrane-penetrating peptide and is effective in delivering phosphorodiamidate morpholino oligonucleotides (PMOs) into eukaryotic cells such as Escherichia coli. It contains 5-carboxyfluorescein (5-FAM), a widely used green fluorescent tag.</p>

<p>Identification of cell penetrating conjugates has aided numerous areas of scientific development. The Drosophila transcription factor Antennapedia contains a homeodomain that can be internalised by cells to the cytoplasm and to the nucleus in a receptor-independent mechanism. The key residues for internalisation have been sequenced (RQIKIWFQNRRMKWKK) and used in several studies to aid entry of recombinant proteins into cells. The peptide sequence described, known as penetratin, was fused to a ligand for Grb-2 resulting in inhibition of downstream Grb-2 signalling events.- Penetratin has also been used in vivo to prime cytotoxic T lymphocytes by conjugating short antigenic peptides to the cell penetrating peptide.On this sequence the N terminal active cysteine has been protected by a 3-Nitro-2-pyridinesulfenyl group. This is a useful modification as it allows this peptide to be used as a carrier peptide in conjugation reactions- this is a particularly useful modification when the peptide-like molecule contains a free thiol group.</p>