Peptides

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.

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.

Balteatide is a novel antimicrobial peptide (AMP) isolated from the skin secretion of wild Peruvian purple-sided leaf frogs,-Phyllomedusa baltea. Balteatide has activity against the Gram-positive bacterium,-Staphylococcus aureus- the Gram-negative bacterium,-Escherichia coli- and the yeast,-Candida albicans- against which, unusually, it is most potent. Bateatide is also devoid of haemolytic activity up to concentrations of 512 mg/L.Balteatide is C-terminally amidated which is common in AMP as it effectively removes a membrane-repelling negative charge and replaces it with a hydrophobic membrane-interacting group. AMPs are a fundamental component of innate immunity/molecular defence across most forms of life and act in a membranolytic fashion to destroy the integrity of microorganisms.Balteatide differs from the myotropic peptide, sauvatide, by just one amino acid (I at position 9 in balteatide and T in sauvatide), however sauvatide displayed little or no antimicrobial activity and balteatide is devoid of myotropic activity.

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 represents the sequence of the 'tethered ligand' and is therefore capable of activating the receptor independently of N-terminal proteolysis.This peptide has been shown to elicit a range of cellular responses including- histamine release from skin mast cells- IL-8 and lactoferrin secretion from peripheral blood neutrophils- increased vascular cell adhesion molecule-1 (VCAM-1) expression- release of IL-8 and granulocyte colony-stimulating factor (G-CSF) from bronchial fibroblasts- secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF), intercellular adhesion molecule 1 (ICAM-1), tumour necrosis factor alpha (TNF-α), matrix metalloproteinase-1 (MMP-1), and MMP-10 from epithelial cells- and production of thymic stromal lymphopoietin (TSLP) in the skin of mice and its release from T cells.PAR activation has been linked to inflammation and an increase in PAR-2 expression is seen in patients with septic shock.- Therefore compounds that-mimic or interfere with the PAR-activating processes are attractive therapeutic candidates.

N-terminal tryptic peptide of parathyroid hormone (PTH), used for quantification and optimisation in LC-MS/MS assays.PTH is an 84-amino-acid polypeptide hormone (PTH 1-84) which is secreted by the parathyroid glands along with its fragments (such as PTH 1-34 and PTH 7-84). PTH increases calcium and decrease phosphate levels in the blood and the abundance of PTH-derived peptides is regulated by blood calcium levels. PTH inhibits the bone growth-promoting activity of osteoblasts and induces osteoclasts to resorb bone and release calcium and phosphate ions into the blood. PTH binds to and activates the receptor parathyroid hormone receptor 1 (PTHR1). PTHR1 is a G-protein-coupled receptor (GPCR) which regulates mineral ion homeostasis, bone turnover and skeletal development

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 &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.

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.

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.

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.

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.

H3 is a core component of the nucleosome, functioning in DNA compaction and availability to transcription machinery. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodelling. 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. There is a wealth of data recording these modifications but understanding their significance is not as clear. In Caenorhabditis elegans H3K23me3 can be induced by exogenous dsRNA and this modification can persist for four generations after the dsRNA exposure has been stopped. H3K23me3 is enriched in C. elegans heterochromatic regions, the histone methyltransferase SET-32, methylates H3K23 in vitro.A 20-mer fragment of the N terminal histone tail is provided here with threonine 22 phosphorylated and lysine 23 tri-methylated (pT22 K23Me3) with an N terminal biotin label attached. The biotin label should allow for easy use in detection by fluorescence microscopy, ELISA or western blots. Alternatively, it can be purified for protein-protein interactions with the appropriate affinity purification protocol.