Peptides

<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>Flagellin is a structural protein which forms the major portion of bacterial flagellar filaments. The N- and C-terminals of flagellin are highly conserved regions, whereas the central core can vary greatly between bacterial species. Flagellin 22 (flg22) is the stretch of amino acids most conserved across bacterial species and is located towards the N-terminal of the flagellin protein.Flg22 is a potent elicitor of plant immune responses and is recognised in plants by the membrane bound leucine-rich repeat-receptor kinase FLAGELLIN SENSITIVE 2 (FLS2). Flg22 induces defence gene expression to trigger both local and systemic immune responses and is thus widely used in plant defence studies.</p>

<p>EC-acid has a formal charge of 0 and a range of biological and chemical uses. CE-acid is also available in our catalogue.</p>

<p>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.</p>

<p>Bombesin was originally isolated from the skin of the european fire-bellied toad (Bombina bombina) and has two known homologues Neuromedin B (NMB) and gastrin-releasing peptide (GRP).Bombesin-like peptides are involved in many physiological functions including: regulation of food intake- anxiety and fear-related behaviour, thermoregulation, stress response, learning and memory and in the stimulation of smooth muscle contraction. Bombesin is also a tumour marker for small cell carcinoma in the lung, gastric cancer, pancreatic cancer, and neuroblastoma.The receptors for these two peptides are known as bombesin receptor type 1 (BB1 also known as NMB receptor) and bombesin receptor type 2 (BB2 also known as GRP receptor). Bombesin shows high affinity to both of these receptor subtypes. These bombesin-like peptides and their receptors are widely distributed in the central nervous system (CNS) and gastrointestinal (GI) tract.This peptide contains an N-terminal pyroglutamyl to prevent the intramolecular cyclisation of the N-terminal of glutamine to N-pyroglutamate (pGlu).</p>

<p>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 trial 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 (2690-2700), has been tested via mass spectrometry to provide a more reliable method of validation of dystrophin levels. Further study with this dystrophin fragment could prove to be a vital step in the understanding and treatment of dystrophin disorders. Within our catalogue we also have other peptides tested for dystrophin quantification available plus the full-length dystrophin protein.</p>

<p>Glucagon (1-29)-[Cys(Cy5)] is derived from glucagon, which is a peptide hormone secreted by alpha cells located in the islet of Langerhans region of the pancreas. Glucagon is an essential catabolic hormone that is responsible for the regulation of blood glucose levels. Once released into the bloodstream, glucagon stimulates the production of hepatic glucose, which means it is considered to be a glucose-mobilizing agent. Excessive levels of glucagon can result in the development of hyperglycaemia, since the action of glucagon results in abnormally high blood glucose levels.This peptide contains Cyanine 5 (Cy5), which is a widely used red fluorescent dye.</p>

<p>Infliximab is a biologic medicine used in the treatment of numerous autoimmune diseases including Crohn disease, rheumatoid arthritis, and ankylosing spondylitis. Infliximab binds with high affinity to tumour necrosis factor-α (TNF-α) blocking most of the cytokine effects, which includes mediating the inflammatory responses. Infliximab is a chimeric human-mouse IgG monoclonal antibody- the constant regions of the heavy and light chains are human-derived. The heavy chain peptide (46-60) has been identified as an antigen for antigen-specific T cell analysis. Numerous methods of immunological analysis can be applied to this peptide to hopefully provide further insight to these autoimmune conditions.</p>

<p>Histone H3 (1-20)-[S]-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 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.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 in this case it 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.</p>

<p>Inhibits the epigenetic reader YEATS domain of the Eleven-nineteen leukemia (ENL) protein and perturbs the recruitment of ENL onto chromatin. Induces downregulation of a set of genes that are essential for leukemogenesis and leukaemia maintenance.</p>

<p>Leptin and melanocortin are well characterised for their roles in energy balance and the regulation of feeding. However, xenin was subsequently isolated from human gastric mucosa and identified as a gastrointestinal peptide hormone. Evidence shows xenin plasma levels rise after meals while administration of xenin leads to feelings of satiation. Unfortunately, the mechanism of xenin regulation on food uptake is still not fully understood. Work has shown xenin negatively effects food intake by a dose dependent manner, the hypothalamus seems to have a key role in this. Furthermore, the signally pathways activated by xenin is independent of those used by leptin or melanocortins. Further work with xenin could provide vital answers to the inhibitory mechanism of this gastrointestinal hormone. It would provide more data to help tackle the ongoing obesity crisis and rise in the number of diabetic patients.</p>

<p>Nangibotide, also referred as LR12, is an antagonist of triggering receptor expressed on myeloid cells (TREM)-1, and was derived from residues 94 to 105 of TREM-like transcript-1 (TLT-1).TREM-1 plays a crucial role in the onset of sepsis by amplifying the host immune response. TLT-1- and TLT-1-derived peptides therefore exhibit anti-inflammatory properties by dampening TREM-1 signalling.  LR12 blocks TREM-1 by binding to the TREM-1 ligand and provides protective effects during sepsis such as inhibiting hyper-responsiveness, organ damage, and death, without causing deleterious effects. The protective effects of modulating TREM-1 signalling are also evident in other models of inflammation such as: pancreatitis- haemorrhagic shock- inflammatory bowel diseases and inflammatory arthritis.</p>

<p>YSA binds to the extracellular domain of ephrin type-A receptor 2 (EphA2) with high affinity and selectivity. YSA binding activates EphA2 and its tumour suppressing downstream signalling pathways (including inhibition of the PI3K/Akt and ERK pathways), and promotes receptor internalisation.EphA2 is highly expressed in many types of solid tumour, and the level of EphA2 expression is positively correlated with malignancy and poor prognosis in some cancer types.YSA has been shown to be an effective targeting peptide of chemotherapeutic drugs to EphA2 expressing tumours. YSA-drug conjugates are able to selectively target EphA2 expressing tumours, both activating tumour supressing downstream signalling pathways, and becoming effectively internalised by cancer cells to further increase the potency of the chemotherapeutic drug. YSA-drug conjugates have been shown to be dramatically more effective at inhibiting tumour growth than chemotherapy alone. Selective tumour targeting with YSA could also reduce the systemic toxicity caused by nonselective and highly toxic chemotherapy agents, and thus reduce adverse side effects of chemotherapy.The uncharged C-terminal amide has the potential to increase the biological activity of this peptide.</p>

<p>PD-1 (27-41) peptide is derived from the programmed cell death-1 (PD-1) which interacts with its ligand, PD-L1 to regulate immune homeostasis. PD-1 and its ligand PD-L1 are critical in regulating T cell activation, tolerance and immuno-pathology. PD-1 is an immune checkpoint and guards against autoimmunity through two mechanisms. First, it promotes apoptosis of antigen-specific T-cells in lymph nodes. Second, it reduces apoptosis in regulatory T cells.Several types of cancer cells overexpress PD-L1 in order to escape from the PD-1/PD-L1 immuno-surveillance mechanism. Consequently PD-1 inhibitors and PD-L1 inhibitors could be used as a therapeutic in the treatment of cancers.</p>

<p>The Histone H3 (20-36)-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.</p>