Peptides

<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-4 agonist peptide represents the N-terminal sequence of the 'tethered ligand' and is therefore capable of activating the receptor independently of N-terminal proteolysis.</p>

<p>Human adrenocorticotropic hormone (ACTH) also known as corticotropin. ACTH 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>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. The functional role of galanin remains largely unknown- however, galanin is predominantly involved in the modulation and inhibition of neuron action potentials. 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) manifests anti-insulin resistance and anti-Alzheimer's disease characteristics and ameliorates or reinforces depression-like behaviour. 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.Galanin (2-30) is provided with an N-terminal 5-FAM, a widely used green fluorescent reagent ideal for peptide labelling and detection and a C-terminal cysteine for site-specific conjugation. The excitation/emission for this reagent is 490 nm/520 nm.</p>

<p>Histone H3 (1-18) 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.</p>

<p>Histone H3 (1-20) K4Me3 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.Lysine 4 of H3 (1-20) has been tri-methylated.</p>

<p>The P11-family of peptides comprises over 20 different peptides which self-assemble into β-sheet structures to form self-supporting isotropic hydrogels under physiological conditions (pH 7.4, 140 mM NaCl). Self-assembling peptides of the P11-family undergo one-dimensional self-assembly, forming single molecule thick, micrometer-long β-sheet nanotapes. Further assembly results in the nanotapes stacking in pairs to form ribbons which further assemble to form fibrils, then pairs of fibrils can entwine to form fibres. Such self-assembling peptides are important biomaterials and may be useful for the development of novel biomaterials for tissue engineering scaffolds and dental enamel remineralisation.</p>

<p>The SOD1 homodimer forms a β-barrel and contains an intramolecular disulphide bond and a binuclear Cu/Zn site in each subunit. This Cu/Zn site holds a copper and zinc ion and is responsible for catalysing the disproportionation of ROS, namely superoxide to hydrogen peroxide and dioxygen. In binding to copper and zinc ions, SOD1 is one of three superoxide dismutases responsible for destroying free superoxide radicals.The clinical relevance of SOD1 is related to its function in regulating ROS in the mitochondria of cells. Most notably, SOD1 is a crucial enzyme involved in ROS release during oxidative stress by ischemia-reperfusion injury, specifically in the myocardium as part of ischemic heart disease. During ischemia reperfusion, ROS release substantially contribute to the cell damage and death via a direct effect on the cell as well as via apoptotic signals. SOD1 is known to have a capacity to limit the detrimental effects of ROS. As such, SOD1 is important for its cardioprotective effects.</p>

<p>Spexin is a neuropeptide encoded by SPX genes, and homologs have been found amongst many vertebrates. The SPX genes encode a preprohormone that leads to the mature hormone spexin, which is highly conserved amongst higher vertebrates. Another form, SPX2, has been identified and named spexin 2. Both sequences of spexin and spexin 2 are highly conserved, suggesting they each play vital roles.Like spexin, spexin 2 is widely expressed in various tissues. This is an amidated spexin-2 (53-70) peptide showing similar biological function to its non- amidated version. Spexin-2, when administered to rats, decreases heart rate and increases urine flow rate. Intraventricular NPQ(53-70) delivery also causes antinociceptive activity in mice's warm water tail withdrawal assay.</p>

<p>Biotin gliadin-derived peptides derived from Gliadin peptides, the component of wheat involved in the gastrointestinal symptoms of wheat allergy and Celiac Disease (CD). During wheat allergies histamines and leukotrienes are secreted due to gliadin peptide sequences cross-linking two IgE molecules on mast cells and basophils.The glutamine and proline rich peptides of which Gliadin is composed of are resistant to proteolysis during digestion, leaving them active in the gastrointestinal tract. Subsequently these are deamidated by tissue transglutaminase and can bind to HLA-DQ2 or DQ8. As a result in patients with the autoimmune disease CD, there is a Th-mediated inflammatory immune response against these gliadin peptides.Gliadin can exert additional effects on the intestinal microbiota and ileal barrier function. It has been found that gut microbiota members such as Bifidobacterium and lactobacillus have the ability to digest and inactivate gliadin peptides hence reducing their inflammatory effects in the gastrointestinal system.Here Biotin (B7) has been added. Biotin is a cofactor for several mammalian biotin-dependent carboxylases which are involved in processes such as gluconeogenesis, amino acid metabolism and fatty acid synthesis.</p>

<p>C5a receptor peptide antagonist which can ameliorate experimentally-induced colon inflammation in mice. It can also reduce fibrillar amyloid deposits, decrease hyperphosphorylated tau levels and rescue cognitive function in a mouse model of Alzheimer's Disease. Also improves hindlimb grip strength and slows disease progression in the hSOD1G93A-mouse model of amyotrophic lateral sclerosis. Orally active and brain penetrant.</p>

<p>Amyloid β 1-15 (Aβ1-15) is one of many short Aβ species found in vivo and is formed by the cleavage of amyloid β precursor protein by β- and alpha-secretase.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.Contains an N-terminal Carboxytetramethylrhodamine (TAMRA) fluorophore. TAMRA is a pH-stable orange-red fluorescenct dye with good photostability.</p>

<p>Human adrenocorticotropic hormone (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. ACTH (15-24) has been shown to be a competitive ACTH receptor antagonist and can be used as a method to combat the overproduction of cortisol. Treatment with ACTH (15-24) inhibits activation of a specific melanocortin 2 receptor (MC2R) by inhibiting adrenocorticotropin hormone (ACTH)-induced production of cortisol. ACTH (15-24) is provided here with a C-terminal cysteine residue for conjugation reactions.</p>

<p>Apidaecin IB was isolated from the honeybee Apis mellifera. As a cationic proline-rich antimicrobial peptide (PrAMP), Apidaecin IB shows sequence homology with drosocin but is devoid of any pore-forming activity. Apidaecin IB is most active against gram-negative bacteria, it can navigate the outer membrane to the periplasm and then to the cytoplasm. Apidaecin IB is a non-lytic AMP, the main target of its antimicrobial activity appears to be inhibition of the chaperone heat shock protein DnaK. Toxicity appears to be exclusively to bacteria and thus has been trialled as a treatment for systemic bacterial infections. Numerous analogues and derivatives are being investigated to establish Apidaecin IB mode of action and also to improve its functionality.</p>

<p>Gag peptide, derived from the simian immunodeficiency virus (SIV), is a homologue of the human immunodeficiency virus (HIV) gag protein which interacts with viral components in order to induce the infectious form of the virus. SIV can be used to model HIV.</p>

<p>Histone H3 (1-20) K4Me3, K9Ac-GG-[Lys(5-FAM)] is derived from Histone 3 (H3) which is one of the four core histones fundamental for compacting eukaryotic DNA into the nucleosome.-Lysine 4 of Histone H3 (1-20) K4Me3, K9Ac-GG-[Lys(5-FAM)] has been tri-methylated, lysine 9 has been acetylated and the C-terminal has been labelled with 5-Carboxyfluorescein (5-FAM), a widely used green, fluorescent tag. Additionally, this peptide contains an uncharged C-terminal amide.LD: Histone H3 (1-20) K4Me3, K9Ac-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. The lysine at position 9 has been acetylated, which neutralizes the positive charge on the amino acid, loosening the chromatin structure. This alteration to the accessibility of chromatin promotes the initiation of transcription.Additionally, Histone H3 (1-20) K4Me3, K9Ac-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>

<p>H1 is the linker histone and is important for chromatin condensation, it binds to the nucleosomal core particles and protects the free linker DNA (ˆ¼20 bp) between each nucleosome. H1 can fine-tune transcription in a locus-specific manner. H1 is involved in several processes, its interaction partners include: pre-mRNA splicing factors- histone chaperones- components of the transcription machinery and DNA-damage response factors. There a 12 subtypes of the H1 linker histone, and they are thought to have specific functions, making H1 the most divergent histone protein family. Like other histones, H1's are extensively post-translationally modified with modifications including: methylation, acetylation, ubiquitination, formylation, poly-ADP ribosylation and phosphorylation.Changes in H1 composition and expression levels are seen in several cancers and other diseases.</p>

<p>The Histone H2A residues 1 to 20 are derived from histone 2A (H2A) 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.At the site of DNA entry on the outer nucleosome, the C-terminus of H2A is present and is able to interact with linker histones or other factors. This allows for variation and changes in nucleosome stability to occur. Furthermore Histone H2A has histone variants such as H2A.Z and H2A.X (which are present in all organisms) and these variants alter the organisation of the DNA.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.Biotin has been added to the lysine on GGK.</p>

<p>Orexin-A (also known as hypocretin-1) is a hypothalamic neuropeptide that regulates feeding behaviour, reward processes, cognition, the sleep-wake cycle and stress. Orexin-A is involved in stress induced mental illness such as major depressive disorder and anxiety disorders and may therefore be a potential target for treatment of these conditions.Orexins are excitatory neuropeptides generated from the prepro-orexin precursor that is exclusively localised in cells of the lateral and posterior hypothalamic region. Orexins are also widely expressed in human and mammalian retinas, such as bipolar cells, amacrine cells and ganglion cells.Orexin-A activates the orphan G-protein-coupled orexin receptor, type 1 (OX1R) and 2 (OX2R). There are approximately 10,000-20,000 orexinergic neurons in the human brain.</p>

<p>LP2</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 (556-570) 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>Pantinin-3, like other pantinin peptides, has high activity against Gram-positive bacteria yet weak activity against Gram-negative bacteria. With the exception of S. aureus, pantinin-3 displays the highest activity against all Gram-negative bacteria for which it has been tested. Pantinin-3 also displays activity against Candida tropicalis and has relatively mild haemolytic activity against human red blood cells.</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). HLA-A is a human MHC class I cell surface receptor and is involved in presenting 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. Hepatitis B virus (HBV) polymerase is a multifunctional enzyme that can use both RNA and DNA as a template for amplification and also has an RNase H function. First the polymerase acts on the HBV pre-genomic RNA (pgRNA) to reverse transcribe it to form the (-) DNA strand. Simultaneously the RNA template is degraded by the polymerases RNase H activity, except for a stretch of RNA at 5' end of the pgRNA which is used to prime the synthesis of the (+) DNA strand. This process results in a new partially double-stranded relaxed circular DNA molecule (rcDNA) within a new capsid.</p>

<p>Residues 1-16 of the gastrointestinal hormone motilin, secreted from endocrine cells in the small intestines, mainly from the jejunum and duodenum, in response to the fasting, drinking water or the mechanical stimulus of eating.</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 TQAFGRRGPEQTQGN (271-285) 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>Boc-VPR-AMC is a fluorogenic peptide substrate composed of the short peptide chain, Valine-Proline-Arginine (VPR) and the fluorophore, 7-amino-4-methlycoumarin (AMC). Fluorogenic peptide substrates such as Boc-VPR-AMC have high sensitivity and specificity and therefore can be used to detect molecules of interest. For example within the field of scientific forensics, Boc-VPR-AMC can be used to investigate deposits of saliva in situ. When Fluorogenic peptide substrates are incubated with specific enzymes, fluorescence is emitted due to the release of the fluorophore from the peptide-fluorophore bond. When Boc-APR-AMC interacts with its target enzyme, the 7-amino-4-methylcoumarin fluorophore is released causing a fluorescent emission at 440nm.</p>

<p>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.</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 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.</p>

<p>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</p>

<p>Bovine myeloid antimicrobial peptide-27 (BMAP-27) belongs to the cathelicidin family of peptides which displays rapid bactericidal activity against Staphylococcus aureus, Streptococcus uberis, and Escherichia coli. Cathelicidins belong to the large group of cationic peptides with amphipathic properties and have an important role in the mammalian innate immune system. BMAP-27 is cytotoxic to human erythrocytes and neutrophils, although at higher than microbicidal concentrations. It has a potential for the treatment of bacterial infections in individuals with cystic fibrosis-associated lung infections.</p>

<p>Orexin B is one of two closely related peptides- the orexins (also known as hypocretins). These small neuropeptides are secreted from orexin-containing neurons, located mainly in the lateral hypothalamus (LH). Orexins function via the binding and activation of two G-protein-coupled receptors (GPCRs)- orexin receptor type 1 (OX1) and 2 (OX2).[Ala(11), D-Leu(15)]orexin-B is a highly potent and selectiveOX2 receptor agonist which can discriminate between the OX1 and OX2 receptors, with a 400-fold selectivity for the OX2 over OX1. [Ala(11), D-Leu(15)]orexin-B is therefore a beneficial tool for addressing the functional roles of OX2.The L-leucine residue at position 11 of orexin B is important for selectivity to OX2 over OX1. L-Alanine substitution at position 11 and D-leucine substitution at positions 15 maintain the potency of orexin-B to OX2, while significantly reducing the potency for OX1.Orexins play several vital roles in a range of physiological activities, including: circadian rhythm- feeding behaviour- energy balance- glucose metabolism- neuroendocrine functions- stress-adaptive responses and reward and addiction. Orexins have also been linked to the pathological processes of neurological diseases such as: narcolepsy- depression- ischemic stroke- drug addiction and Alzheimer's disease.</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)alanine residues as acyl acceptors, 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>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 (371-382) 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>C-type natriuretic peptide (CNP) is expressed from numerous tissue types but primarily within the central nervous system and the bone. CNP binds the natriuretic peptide receptor B (NPR-B) and acts as an autocrine/paracrine factor. CNP signalling acts as a positive regulator of endochondral bone growth. Both CNP and NPR-B are being explored as therapeutic targets for growth disorders including achondroplasia. CNP (1-22) is the major form of CNP found in the plasma. Exogenous CNP (1-22) can be cleared quite effectively, administration of a constant 'high' dose was able to overcome this obstacle to induce endochondral ossification and accelerated bone growth. However, CNP (1-22) may have the potential to induce systemic vascular resistance and blood pressure issues which would need to be addressed before future clinical applications. Researchers are trying to better establish the function and role of CNP (1-22) one strategy has been the addition of conjugates, such as the C-terminal of ghrelin, to try and improve the clinical efficacy.</p>

<p>Fluorescence resonance energy transfer (FRET) peptide substrate derived from SARS-CoV-2 spike (S) S1/S2 site. This FRET peptide exhibits internal fluorescence quenching when intact, however hydrolysis of the peptide between the donor/acceptor pair generates fluorescence, enabling the quantitative measure of enzymatic activity. The S1/S2 site of SARS-CoV-2 S is efficiently cleaved by a wide range of proteases including furin.SARS-CoV-2 Spike (S) protein is one of the four essential structural proteins from the coronavirus SARS-CoV-2. S protein is a large, class I viral transmembrane protein essential for viral entry into the cell via binding to the host angiotensin-converting enzyme 2 (ACE2) receptor. S assembles as a trimer on the surface of the virion, giving it its distinctive 'corona' or crown-like appearance. The ectodomains of S proteins are divided into two subunits, S1 and S2. S1 helps in host receptor binding and is further divided into two subdomains: N-terminal domain (NTD) and C-terminal domain (CTD), both of which act as receptor-binding domains. The S1 CTD contains the receptor-binding motif (RBM). The S2 subunit accounts for fusion. Peptide contains an N-terminal 5-carboxyfluorescein (5-FAM), a widely used green fluorescent tag and a 2, 4-dinitrophenyl (Dnp) quencher.</p>

<p>Reactivity to human leukocyte antigens (HLAs) is a risen concern in clinical treatments such as organ transplant rejection. Understanding the epitopes causing reactivity and the signalling pathways could lead to better clinical therapies. 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. The HS1 fragment (160-168) 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. HS1 fragment (160-168) 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>Myelin oligodendrocyte glycoprotein (MOG) is a member of the immunoglobulin (Ig) protein superfamily and is expressed exclusively in the central nervous system (CNS) on the surface of myelin sheaths and oligodendrocyte processes. MOG is expressed at the onset of myelination, and therefore is a potential marker for oligodendrocyte maturation.MOG contains an extracellular domain, a transmembrane domain, a cytoplasmic loop, a membrane-associated region and a cytoplasmic tail. MOG may function as a cell surface receptor or cell adhesion molecule. Fifteen different alternatively spliced isoforms have been detected in humans. These are present either on the cell surface, the endoplasmic reticulum in the endocytic system, or in secreted form.The secreted form of MOG may trigger autoimmunity if released into the cerebrospinal fluid and periphery. MOG is thought to be a key target for autoantibodies and cell-mediated immune responses in inflammatory demyelinating diseases such as multiple sclerosis (MS) and is therefore widely studied in this field.The MOG (34-56) fragment is in the most potent auto-antigenic region of MOG, and is highly effective at inducing experimental autoimmune/allergic encephalomyelitis (EAE), an animal model that resembles MS. This peptide has an uncharged C-terminal amide.</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 western blot, mass spectrometry, immunostaining and RT-PCR to try and provide the most robust method of validation of dystrophin levels possible. 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>CREB is a transcription factor that regulates diverse cellular responses including: proliferation- survival and differentiation- adaptive immune responses- glucose homeostasis- spermatogenesis- circadian rhythms and synaptic plasticity associated with memory. CREB is induced by a variety of growth factors and inflammatory signals and subsequently mediates the transcription of genes containing a cAMP-responsive element, including IL-2, IL-6, IL-10, and TNF-alpha. In the immune system, CREB induces an anti-apoptotic survival signal in monocytes and macrophages, has a role in promoting the proliferation, survival and regulation of T and B lymphocytes and is required for the generation and maintenance of regulatory T cells. CREB also often promotes anti-inflammatory immune responses, such as through the inhibition of NF-KB activity, the induction of IL-10, and the generation of Tregs. These anti-inflammatory responses could be protective by inhibiting unwanted inflammation, tissue damage, and autoimmune responses, or they could be pathogenic in the context of infection and tumour immunosurveillance. Peptide is labelled with an N-terminal 5-carboxyfluorescein (5-FAM), a widely used green fluorescent tag.</p>

<p>CBL (167-180) is derived from the CBL E3 ubiquitin ligase which targets receptor tyrosine kinases to lysosome degradation. CBL and its family member CBL-B are expressed in hematopoietic cells and as E3 ubiquitin ligases they contain a tyrosine kinase domain and an RF domain joined by a linker domain. The function of the RF domain is to transfer ubiquitin from E2 ubiquitin-conjugating enzymes onto the target protein which is often phosphorylated. Consequently the ubiquitinated substrate, the receptor tyrosine kinases, are ultimately targeted to the lysosome for degradation.EGFR is an example of a receptor tyrosine kinase whose activation is prevented by CBL and CBL-B when they bind and recruit GRb2, the adapter protein to EGFR. Consequently the ubiquitinylation of EGFR occurs and targets it for recognition by the endosomal protein complex and then lysosome degradation.It has also been found that the CBL family can negatively regulate through ubiquitinylation, PI 3-kinases, Rap G-protein guanine nucleotide exchange factor (GEF), C3G and Rho GTPase GEF Vav which are all non-receptors.If CBL becomes non-functional it can be associated with malignancies such as acute myeloid leukemia and myelodysplastic syndrome.</p>

<p>Relaxin-3 is part of the insulin/relaxin superfamily with various roles, including appetite, stress, and addiction. Relaxin-3 binds to its cognate receptor relaxin family peptide 3 receptor (RXFP3). B1-22R  is a single-chain relaxin-3 antagonist for RXFP3 no interaction is found with RXFP1 or RXFP4. B1-22R  is a truncation of the B-chain of relaxin-3 and the addition of an arginine residue at the C-terminus-B1-22R acts as a RXFP3 antagonist. B1-22R has been used to perform structural analysis relationships (SARs) and residue scanning to understand the critical residues and conformation of the interaction between B1-22R and RXFP3. B1-22R can generate more potent analogs of relaxin-3 that are more stable and serve as models for drug design targeting the relaxin-3 receptor for regulation of addiction, stress, and appetite.B1-22R is provided in the amide form.</p>

<p>Soybean trypsin inhibitor inhibits trypsin, factor Xa, plasmin, and plasma kallikrein activity in serum-free cell culture media. It does not inhibit metallo-, cysteine, aspartic proteases, or tissue kallikrein (serine proteases).Kallikreins (KLKs) are a large family of secreted serine proteases with either trypsin-like or chymotrypsin-like specificity which carry out many biological functions. The KLK proteases are involved in pathways that regulate skin desquamation, tooth enamel formation, kidney function, seminal liquefaction, synaptic neural plasticity, and brain function. Disruptions in the function of KLK activity has been linked to several pathologies, including respiratory diseases, neurodegeneration, anxiety, schizophrenia, skin-barrier dysfunction, pathological inflammation, and cancer.</p>

<p>Galanin is a neuropeptide synthesised and released by the brainstem locus coeruleus (LC). Galanin is expressed in most LC neurons in rodents and humans. Galanin has been shown to inhibit LC activity by hyperpolarising LC neurons, suppressing their spontaneous firing rate, and enhancing alpha2-adrenergic receptor-mediated negative feedback. Galanin is also a potent trophic and neuroprotective factor throughout the nervous system.Galanin is widely distributed from the central nervous system, peripheral regions and endocrine system. 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 which are G protein-coupled receptors and 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 Gα pathway, activation of the receptor leads to cellular influx of K+. Each receptor has been associated with neurological diseases such as GalR3 and epilepsy.Galanin protects against a variety of physiological insults in vitro, including excitotoxicity and β-amyloid toxicity. Changes in galanin have been widely studied in relation to Alzheimer's disease and galaninergic neurons have been shown to be spared in late-stage Alzheimer's relative to non-galaninergic neurones.</p>

<p>PTH 1-34, is a biologically active peptide fragment of parathyroid hormone (PTH). PHT 1-34 has been shown to enhance bone fracture healing by promoting osteogenesis. PTH 1-34 also has chondrogenic properties.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.</p>

<p>Syntide-2 is a substrate peptide which was specifically designed to be homologous to site 2 in glycogen synthase. Syntide-2 is therefore phosphorylated by Ca2+ calmodulin-dependent protein kinase II as well as other calcium dependant kinases and protein kinase C. Synthase-2 can also be phosphorylated by CAMP-dependent protein kinase and to a lesser extent- phosphorylase kinase, but not by myosin light chain kinase.</p>

<p>SARS-CoV-2 Membrane protein (172-188)</p>

<p>Binds to human transferrin receptor (TfR). This 12-amino acid peptide does not compete with transferrin for receptor binding and is able to internalise into TfR expressing cells.</p>

<p>SAMS peptide was originally designed as a selective substrate for mammalian 5' adenosine monophosphate-activated protein kinase (AMPK) for use in kinase assays. However it is also able to be phosphorylated by the yeast AMP homologue- sucrose non-fermenting 1 kinase (SNF1) and SNF1-related kinases (SnRK1) in plants.The conserved family of kinases containing SnRK1, SNF1 and AMPK plays an important role in regulating cellular energy homeostasis.</p>

<p>Histone H3 (1 - 21) K4Me3 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.Lysine 4 of Histone H3 (1 - 21) K4Me3 has been tri-methylated.</p>

<p>SARS-CoV-2 ORF3a (26-40)</p>

<p>ANP (1-28) is derived from the atrial natriuretic peptide (ANP) which is a cardiac hormone involved in maintaining cardio-renal homeostasis. This occurs through the activation of the guanylyl cyclase-coupled receptor, resulting in the increased concentration of cyclic guanylate monophosphate. Moreover its function in the processes of anti-proliferation and anti-angiogenesis allow it to take part in cardiovascular remodelling.ANP is a member of the natriuretic peptide family and it is encoded by the NPPA gene, located on chromosome 1. Once synthesized from the 151 amino acid pre-prohormone into its biologically active form, ANP is secreted by the atrial cardiomyocytes in the circulating forms: ANP (1-98) and ANP (99-126). This synthesis process involves the signal peptide being removed from the pre-prohormone resulting in pro-ANP (1-126) which is converted into the circulating forms by the type II transmembrane serine protease Corin.</p>