Peptidi

<p>Natalizumab LC46-58 KGN deimmunised</p>

<p>Native Melan-A (26-35) decapeptide derives from the melanocyte lineage-specific protein Melan-A/MART-1, which is expressed in almost 75-100% of primary and metastatic melanomas.<br>The region 26-35 of Melan-A protein acts as an antigenic peptide that is recognized by CD8+ tumor-reactive cytolytic T lymphocytes (CTLs) for designing antigen-specific cancer vaccines1. It has been shown that CD8+ Melan-A-specific CTLs isolated from melanoma patients efficiently lyse the Melan-A-expressing HLA-A*0201+ melanoma cell line. However, CTLs preferentially recognize the Melan-A (26-35) peptide as compared with the Melan-A (27-35) peptide. Moreover, the Melan-A (26-35) A27L analog (ELAGIGILTV) has a higher binding affinity to HLA-A*0201 than the native Melan-A (26-35) peptide (EAAGIGILTV), and consequently displays more potent antigenicity and immunogenicity.<br>It has been reported that the concentration of Melan-A (26-35) A27L analog required to obtain 50% of maximal antigenic activity (EC50) is 0.01nM, whereas that of the native Melan-A (26-35) peptide is 0.25nM1. Therefore, the relative activity of Melan-A (26-35) A27L analog is 25 fold higher than that of the native Melan-A (26-35) peptide.<br>Furthermore, functional competition assay has shown that the concentration of Melan-A (26-35) A27L analog required to achieve 50% inhibition (IC50) of tumor lysis is 2nM, which is 10 fold lower than that of the native Melan-A (26-35) peptide. Regarding peptide stability in human serum, the half-lifes (t1/2) of the native Melan-A (26-35) peptide and the A27L analog are quite similar (45 and 40min, respectively) as measured by HPLC-ESI-MS, but much higher than that of the Melan-A (27-35) nonapeptide (5min).</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>Transportan is an amphipathic 27 amino acid peptide that was generated from 12 functional amino acids of galanin and 14 amino acids of mastoparan connected via a lysine residue. Transportan has been functionally characterised as a cell penetrating peptide (CPP) that does not appear to be mediated by endocytosis. All cell types tested were permeated by transportan, initially localising to the outer membrane it then travels to cytoplasmic membrane structures and eventually perfuses to the nucleoli. This CPP has been used for numerous applications and assays to great effect including indirect immunofluorescence and drug delivery.TP reveals some characteristic features of both galanin and mastoparan since it inhibits the binding of galanin to GALR-1 receptor as well as modulates the activity of G proteins due to the inhibition of GTPase activity.</p>

<p>Ghrelin is involved in several physiological processes, including feeding and lipid accumulation, stress response, anxiety, cardiac performance, immunity and inflammation, taste sensation, reward-seeking behaviour, regulation of glucose metabolism and thermogenesis, memory, motivation and learning.Ghrelin is a peptide hormone that typically has a serine at the third residue and relies on modification with a fatty acid to give ghrelin its functional activity. In its modified form, ghrelin is an endogenous ligand for the pituitary gland's growth hormone receptor (GHS-R) and stimulates growth hormone release. Rat/mouse ghrelin differs from the human form at positions 11 and 12 (RV) in rats to (KA) in humans.Ghrelin acts on the hypothalamic arcuate nucleus as an orexigenic agent to stimulate appetite. Ghrelin is produced in the stomach as a precursor peptide preproghrelin, cleaved to ghrelin. Ghrelin circulates in the blood and can cross the blood-brain barrier. Levels of ghrelin respond to fasting conditions and allow signals about the energy status to be transmitted from the peripheral organs to the central nervous system to maintain energy homeostasis.Ghrelin is a valuable target for treating conditions such as anorexia, cachexia, sarcopenia, cardiopathy, neurodegenerative disorders, renal and pulmonary disease, gastrointestinal disorders, inflammatory disorders and metabolic syndrome.</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.This peptide contains a covalently bonded N-terminal Biotin tag that can be used for detection and purification.</p>

<p>A hydroxyproline glycine peptide in acid form. This peptide is a substrate for prolyl dipeptidase. Ingestion of the Hyp-Gly dipeptide can improve skin conditions. Hyp-Gly ingestion improves facial skin moisture and elasticity and reduces facial aging. Additionally, Hyp-Gly enhances fibroblast proliferation.</p>

<p>Glucagon-like peptide (GLP) 1 is a post-translationally modified version of proglucagon. GLP-1 (1-37) is a naturally produced analog of GLP-1. Unlike truncated GLP-1, GLP-1 (1-37) does not alter food intake in rat models or pancreatic insulin secretion. GLP-1 (1-37) can induce insulin production in developing adult intestinal cells via upregulation of the ngn3 gene and its downstream targets. This can restore glucose homeostasis when implanted into diabetic mice. GLP-1 (1-37) may offer a  future treatment for diabetes mellitus. GLP-1 (1-37) can also inhibit chemokine-induced migration of human CD4-positive lymphocytes, an early step in atherogenesis. This raises the possibility that GLP-1 (1-37) is part of a novel mechanism to modulate vascular disease.</p>

<p>Ovalbumin (OVA) is the primary protein in egg-white, and is involved in initiating food allergies and asthma. It is a highly immunogenic protein and can be used for peptide conjugation in the development of antibodies.OVA (251-264) is a class I (Kb)-restricted peptide epitope of OVA. The ovalbumin fragment is presented by the class I MHC molecule, H-2Kb.</p>

<p>Histone H3 (1-22) K9Me1-Biotin is derived from Histone 3 (H3) which is one of the four core histones (H2A, H2B, H3 and H4) fundamental in compacting eukaryotic DNA into the nucleosome. The nucleosome arises when 147 base pairs of DNA wrap around a H3-H4 tetramer and two H2A-H2B dimers, forming the histone octamer core. Both H4 and H3 are highly conserved and perform roles in binding to segments of DNA which enter and leave the nucleosome and in chromatin formation. Similar to the other core histone, H3 has a globular domain and a flexible N-terminal domain, 'histone tail' which can undergo modifications such as acetylation, methylation, phosphorylation and ubiquitination. Due to histones containing a large number of lysine and arginine residues they have a positive net charge which interacts in an electrostatic manner with the negatively charged phosphate groups in DNA. The transcriptional activation or silencing of the chromatin is controlled by ATP-dependent chromatin remodelling factors and histone modifying enzymes which target histone proteins. Both processes function to alter the positioning of the nucleosome, allowing the DNA it to be either available or inaccessible to the transcription machinery.Another modification process histones can undergo is biotinylation where the covalent attachment of a biotin molecule is catalysed by the enzyme Biotinidase. This cleaves biocytin to generate a biotinyl-thiester intermediate. The biotinyl can then be transferred onto the histone lysine ɛ-amino group which 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>ORF7a is an accessory protein that is key to SARS-CoV-2 evading the immune system. ORF7a acts on the secretory pathway to lower surface MHC-I expression by specifically interacting with the MHC-I heavy chain and delaying its export from the endoplasmic reticulum. These factors make the ORF6 protein a viable target for developing new antiviral drugs. In addition, the identification of epitopes within the ORF7a-10 protein 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. ORF7a-10 protein (69-86) 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>Gene therapy is potentially an ideal treatment for muscle tissue myopathies but targeting remains an issue. The large volume of muscle in the body versus the requirement for tissue-specificity is of particular concern. This heptapeptide has been shown to preferentially bind myofibers and thus can be used to study targeting of peptide/gene- delivery to muscle tissue. Research into gene therapy of Duchenne muscular dystrophy (DMD) and Spinal muscular atrophy (SMA) has been of particular interest with muscle targeting peptides.- This product has been shown to orientate to muscle and heart tissue and when conjugated to a phosphorodiamidate morpholino oligomer (PMO)-increases dystrophin expression by 25%. This product already shows ideal placement to continue cardiac research to overcome some of these issues.</p>

<p>Selective peptide ligand for FRalpha, demonstrating specific binding to FRalpha expression cells and tumour targeting ability in vivo.</p>

<p>Galanin is a widely distributed neuropeptide in the central nervous system (CNS), 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 which are 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 potassium ions.The galanin active N-terminal fragment (1-16) has been identified as a highly potent agonist for the galanin receptors.  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. Galanin fragments have different affinities for GalR receptors. Galanin (1-13) has been shown to act as a high-affinity receptor antagonist in competitive receptor displacement tests using rats. Numerous chimeric peptides have been generated with galanin (1-13) to generate peptides for studying galinergic signalling. Examples of chimeric peptide tools used with galanin (1-13) are the neuropeptide Y fragment (named M32) and a bradykinin fragment (called M35).</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 trials including antisense oligonucleotide exon skipping and gene therapy. However, the efficacies of these treatments are not easily quantified. Currently levels of muscular dystrophin are quantified by western blot which can be unreliable. The peptide provided here, aligning residues dystrophin (396-405), has been shown to provide absolute quantification of dystrophin levels from biopsies using parallel reaction monitoring. This will hopefully allow better management of dystrophin disorders with better quantifications tools based on dystrophin (396-405). 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>The dodecapeptide AR71 prevents melanoma inhibitory activity (MIA) dimerisation and hence inhibits (MIA). It therefore has the potential to be used as a therapeutic in melanoma.</p>

<p>Cell-permeable calmodulin (CaM) agonist that binds to the EF-hand/Ca2+-binding site and can activate phosphodiesterase in the absence of Ca2+ and inhibit Ca2+ mediated cytotoxicity and apoptosis.</p>

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

<p>Galanin is predominantly an inhibitory neuropeptide expressed in humans and other mammals' brains, spinal cords, and gut. Galanin signalling occurs through three G protein-coupled receptors GalR1-3. Galanin has been implicated in many biologically diverse functions, including nociception, waking and sleep regulation, cognition, feeding, mood regulation and blood pressure regulation. Galanin appears to have neuroprotective activity as its biosynthesis is increased 2-10 fold upon axotomy and during seizure activity in peripheral tissues and the brain.The clinical relevance of galanin is related to several chronic neural disorders, including Alzheimer's disease, epilepsy, depression and cancer- those who suffer from type 2 diabetes mellitus, depression and Alzheimer's disease often express high levels of galanin. Conversely, intervention with galanin agonists (for example, M617, M1145 and M1153) were able to ameliorate disease symptoms such as Alzheimer's and have pro-nociceptive effects. Specifically, activation of GAL2 can alleviate such disease features in human and rodent models. This galanin (2-30) peptide has been used to characterise Galanin's binding sites and affinity for GALR receptors via competition binding analysis. Galanin (2-30) is a full agonist of the GALR2 receptor compared to its affinity for GALR1.</p>

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