Peptidi

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

<p>SMAP -18 is a truncated form of sheep myeloid anti-microbial peptide-29 (SMAP-29). SMAP-29 displays extremely high anti-microbial activity against fungi and gram-negative bacteria including Pseudomonas strains and multidrug-resistant pathogens, however it also has high cytotoxic activity to human cells. The carboxyl terminal is more hydrophobic and may be responsible for higher hemolytic activity of SMAP-29, whereas the anti-microbial activity has been attributed to the N-terminal amphipathic alpha-helix region (residues 1-18). SMAP-18 displays much higher cell selectivity as compared to parental SMAP-29 because of their decreased hemolytic activity and retained anti-microbial activity.The cathelicidins are a large family of structurally diverse host defence peptide (HDP- formerly called antimicrobial peptides) found in mammalian species including humans. All members of the cathelicidin family contain an N-terminal cathelin domain and a C-terminal domain of varied structure that displays anti-microbial activity.</p>

<p>BRAF dimers are a core component of the MAPK cascade to pass extracellular stimulus signalling to the nucleus. However, BRAF is also the most often mutated kinase in human cancers resulting in hyperactivation of signalling. BRAF inhibitors are thus a target for cancer therapy treatments.Braftide is a decamer of BRAF sequence found in the dimer interface. It binds allosterically to BRAF preventing kinase activity of mono/dimeric forms. It also leads to the degradation of BRAF and downregulation of MAPK signalling. This creates an ideal dual function inhibitor of a key kinase in cancers such as metastatic melanoma.</p>

<p>Flexible Glycine Linker (3 x GGGGS)</p>

<p>Amphipathic helical peptide derived from the chimeric PPTG1 peptide and labelled at the N-terminus with fluorescein.</p>

<p>[BDP630/650]3-halphaCGRP (calcitonin gene-related 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>TMPRSS4 (199-207) fluorogenic peptide</p>

<p>Novel cell-penetrating peptide (CPP). M918 was derived from the tumour suppressor protein p14ARF and can be utilized for both covalent and non-covalent delivery of macromolecules in animal and plant cells. CPPs are able to cross the cell membrane at low micromolar concentrations without causing significant membrane damage in vivo and in vitro.This cationic CPP Peptide is labelled with an N-terminal 5-carboxyfluorescein (5-FAM), a widely used green fluorescent tag.</p>

<p>Substrate of the epidermal growth factor receptor (EGFR), a member of the receptor tyrosine kinase family known as ErbBs or HER receptors. These receptors are involved in the regulation of cell proliferation, survival, differentiation and migration. However their dysregulation can contribute towards many diseases such as cancer.Binding to the ligand binding domain of the EGFR causes receptor dimerization. This is sequentially followed by the tyrosine kinase domain being activated and the tyrosines on the C-terminal tail become phosphorylated, which in turn activates downstream signalling pathways.</p>

<p>This C-terminal Sortagging peptide acts as a (oligo)glycine nucleophile in the final steps of a sortagging protein labelling reaction. This reaction results in the (Sulfocyanine7) fluorescent moiety being attached to the C-terminus of the target protein or peptide.A substrate peptide containing the LPXTG motif 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 of the substrate peptide. Cleavage results in the formation of a thioacyl intermediate between the substrate peptide and SrtA. This intermediate is then resolved by the N-terminus of this (oligo)glycine nucleophile peptide, resulting in the creation of a new peptide bond that links the substrate peptide to this peptide and its fluorescent dye.  This method of protein labelling is known as sortagging.This peptide contains Sulfocyanine7, which is a NIR (near infrared) emitting fluorescent dye.</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>Melanoma-associated antigen As (MAGEA) are a large family of tumour-associated antigens and a subclass of the larger family of cancer testis antigens (CTAs). These proteins are tumour antigens expressed in a variety of malignant tumours including: bladder- lung- skin and breast malignancies. In healthy tissue however their expression is restricted to germ cells of the testis, nervous system, foetal ovaries and placenta. In cancer cells, the MAGEA family proteins support growth, survival and metastasis, and contribute actively to malignancy. They are also involved in the regulation of the tumour suppressor protein p53 pathway and in regulating ubiquitin signalling in cancer cells. MAGEA expression is linked to poor prognosis in cancer patients. MAGEA subfamily proteins are recognized by cytotoxic T lymphocytes and evoke a strong T cell reactivity against autologous tumour cells in culture.</p>

<p>123B9.</p>

<p>Cathelicidin-related anti-microbial peptide (CRAMP), is the mouse homologue of the human LL-37 antimicrobial peptide and shares 67% sequence identity with LL-37.CRAMP-18 is the anti-bacterial sequence derived from CRAMP, it possesses potent anti-bacterial activity against Gram-positive and Gram-negative bacterial strains with no haemolytic activity. As well as displaying direct anti-microbial activity, CRAMP-18 also binds to lipopolysaccharide (LPS) to neutralise LPS activity.CRAMP is a cationic peptide, encoded for by the Camp gene and is highly expressed in bone marrow. Its expression is up-regulated by infectious and inflammatory signals and it is secreted by cells such as neutrophils, epithelial cells, and macrophages.</p>

<p>PD-1 inhibitors and PD-L1 inhibitors are a group of checkpoint inhibitors being developed for the treatment of cancer.PD-1 and its ligand PD-L1 are critical in regulating T cell activation, tolerance and immunopathology. 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 immunosurveillance mechanism. In this way, Human PD - L1 inhibitor V could be used in the treatment of cancers that overexpress PD-L1.</p>

<p>Peptide derived from the variable region on the heavy chain of immunoglobulin (Ig) which is part of the fragment antigen binding (Fab) fragment of antibodies. Ig or antibodies are made up of two heavy and two light chains both of which have a constant region and a variable region. The variable region, the antigen binding site, is composed of three complementarity determining regions (CDRs) from the variable heavy chain and three CDRs from the variable light chains. The amino acid sequences of the variable region differ between each antibody allowing Ig to bind to specific antigens.The variable regions are encoded by a variety of V, D and J gene segments. During somatic recombination different combinations from the V, D and J varieties can be joined together. Consequently this gives rise to a diverse variable region.The Ig heavy chain can be classed as being either: IgM, IgG, IgA, IgD or IgE each of which change the function of the antibody.</p>

<p>Albumin (318-328) Bovine is derived from the globular protein Albumin and is found in the blood plasma of humans (known as Human Serum Albumin, HSA) where it serves to maintain plasma pressure and nutritional balance. Another role it carries out is the transportation of bound molecules through the blood. Bovine serum albumin (BSA), composed of 583 amino acids, is very similar to HSA thus allowing BSA to be used as a successful model and a standard protein in laboratory experiments.Although BSA and HAS share homology in their three domains, I, II and III, BSA contains 2 tryptophan whereas HAS only contains 1 tryptophan residue.In agriculture the presence of the albumin protein has been used to assess the health of cows to ensure that a suitable quality of milk and meat are produced. Moreover it is important to detect bovine albumin in food and pharmaceutical products due to it being an allergenic protein.</p>

<p>T regulatory cell epitopes (Tregitopes) are a set of natural T cell epitopes derived from immunoglobulin G. These peptides are Treg-activating and show some promise in prophylactic and therapeutic studies in type 1 diabetes mellitus: which is associated with effector T cell (Teff) destruction of insulin-producing pancreatic β-islet cells. In non-diabetics, self-reactive T cells are deleted during thymic development, rendered anergic, or converted into natural regulatory T cells (Tregs) that suppress autoimmune responses.Tregitopes are processed and presented by MHC class II molecules. They can suppress effector T cell responses, and up-regulate Treg-associated cytokines and chemokines. Tregitopes help stimulate 'antigen-specific adaptive tolerance induction' (ASATI) to modulate antigen-specific transplant rejection and to reduce immune responses to allergens in vitro and in vivo. Tregitope 289 is also available in our catalogue.</p>

<p>ANP (1-23) 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>

<p>G protein-coupled receptor 56 (GPR56/ ADGRG1) is a novel and evolutionarily conserved regulator of peripheral nerve development and function, with important implications for human health and disease.During Schwann cell (SC) development, GPR56-dependent RhoA signalling promotes timely radial sorting of axons. In the mature peripheral nervous system (PNS), GPR56 is localised to distinct SC cytoplasmic domains. Here it is required to establish proper myelin thickness, and facilitate organisation of the myelin sheath.</p>

<p>Simian immunodeficiency virus (SIV) has been used as a model in rhesus monkeys to understand human immunodeficiency virus (HIV) viral life cycle and lead towards drug development. HIV specific CD8+ T-cell (cytotoxic T lymphocyte (CTL)) responses are important in the control of viral replication. Inducing a sustained HIV-1 specific CD8+ T-cell response is the target for vaccine development by using conserved HIV-1 epitopes. The HIV gag gene encodes p17 and p24. Capsid protein p24 forms the conical core of the virus that encapsulates the genomic RNA-nucleocapsid complex. SIV encode a homologous Gag peptide, this allows use of rhesus monkey models to better understand the immune response to SIV/HIV.A CTL recognition epitope of SIV p24 Gag, residues TPYDINQML, activates the immune response. SIV Gag peptides have been used as effective epitopes in immunological assays to assess CTL response. Stimulation of rhesus monkey cells with TPYDINQML epitope triggers CD8+ T lymphocytes to produce soluble factors (β-chemokines) that inhibit SIV replication. Further work may lead towards a HIV vaccine using the Gag epitopes.</p>

<p>Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein found in all prostate tissue- androgen levels negatively regulate its expression. PSMA expression correlates with cancer aggressiveness and represents an independent indicator of poor disease outcomes. PSMA is being explored as a clinical biomarker to allow differentiation of aggressive prostate cancers from other cases using imaging and RT-PCR.The epitope PSMA (35-40) is from the splice isoform PSMA-1. There has been progress in generating PSMA targeting radioligands as a therapy for various cancers. θ and β radiation probes such as 177Lu-PSMA-617 have been developed and shown in trials to be clinically effective treatments against metastatic prostate cancer. Other studies have tested the PSMA targeting radioligands efficacy against triple-negative breast cancer cells. Further work with the PSMA (35-40) epitope could help progress the outlook for these aggressive cancers.</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>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. Melanoma-associated antigen 1 (MAGE-A1) is part of a well-characterized group of cancer/testis antigens (CTA) that are encoded as a separate cluster on the X chromosome. MAGE-I antigens are mainly expressed in highly proliferating cells, such as cancer cells and therefore may be ideal targets for cancer immunotherapy. Expression of MAGEs has been reported several types of cancer including: lung- breast- thyroid- colon- stomach- liver and bladder where MAGE-A is considered to be a poor prognostic factor.This peptide corresponds to part of the MAGE-A1 sequence which is presented on the MHC class I antigen HLA-A*02.</p>

<p>Histone H3.3 is a replication-independent histone variant, which replaces canonical histone H3.1/2 outside of S phase. H3.3 is expressed throughout the cell cycle, as well as in quiescent cells and is referred to as the 'replacement histone'. H3.3 is largely deposited in a DNA synthesis-independent fashion by a distinct set of chaperones proteins. H3.3 accumulates in post mitotic cells, such as cerebral cortical neurons and is incorporated at sites of UV damage where it protects against sensitivity to UV light. H3.3 deposition occurs on DNA sequences that are transiently nucleosome-free, such as during transcription and DNA repair, therefore serving as a marker for regions of high transcriptional activity. H3.3 is also enriched in heterochromatic subtelomeric and pericentromeric regions. H3.3 plays important roles in many developmental contexts such as in stem cells, during fertilization and reproduction and during reprogramming of genomes following fertilization or somatic cell nuclear transfer. Mutations in histone H3.3 are common events in certain cancers.</p>

<p>The renin angiotensin system (RAS) consists of many angiotensin peptides involved in regulating functions such as blood pressure, cardiovascular function and energy balance. RAS activity is elevated in obesity and RAS is widely studied in relation to lifestyle-related diseases.Angiotensin 1-7 (Ang-(1-7)) is a component of the RAS. Ang-(1-7) is produced by angiotensin-converting enzyme 2 (ACE2), from the angiotensin II (Ang-II) peptide, as well as by prolylendopeptidase (PEP) and neutral endopeptidase (NEP) which produce Ang1 7 directly from angiotensin I (Ang-I).Ang-(1-7) broadly opposes Ang-II actions. Ang-(1-7) has vasodilatory and anti-oxidative effects, and exerts protective actions in hypertension, diabetes, and other cardiovascular disorders, Ang-(1-7) therefore represents a promising therapeutic target for cardiovascular and metabolic diseases. Ang (1-7) exerts its actions via its G-protein-coupled receptor, Mas. This novel arm of the RAS has effects that counterbalance those mediated by the classical ACE/Ang-II pathway.The C-terminal proline fro this peptide is in the D enantiomer.</p>

<p>An agonist of anti-TNFalpha-induced apoptosis (ATIA) whose function is to provide cells with protection from TNFalpha and hypoxia-induced apoptosis. It has been labelled with tetramethylrhodamine (5-TAMRA).</p>

<p>[β-Ala]-[Lys(5-TAMRA)]-acid</p>

<p>Histone 4 (H4) is one of the four core histones (H2A, H2B, H3 and H4) which are essential for compacting eukaryotic DNA into the nucleosome. Due to the high lysine and arginine content, histones have a net positive charge and therefore electrostatically interact with negatively charged DNA. 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. Like other core histones, H4 has a globular domain and a flexible N-terminal domain, the histone tail, which can undergo modifications such as acetylation, methylation, phosphorylation and ubiquitination.Gene transcriptional activation or inactivation is controlled by ATP-dependent chromatin remodelling factors and histone modifying enzymes. Both processes function to alter the positioning of the nucleosome, allowing the DNA within to be either accessible to the transcription machinery or inaccessible. H4 lysine rich tail plays a role in the higher order chromatin folding.</p>

<p>Alyerserin-1a is a C-terminally α-amidated 23 residue cationic antimicrobial peptide (AMP). Antimicrobial peptides (AMPs) are produced by the innate immune system and are expressed when the host is challenged by a pathogen. The Alyerserin family of peptides was first identified in norepinephrine-stimulated skin secretions of the midwife toad-Alytes obstetricans-(Alytidae). Alyteserin-1 peptides have limited structural similarity to the ascaphins from the skins of frogs of the Leiopelmatidae family. Alyteserin-1 peptides are selective at inhibiting growth activity of Gram-negative bacteria-such as Escherichia coli and Salmonella-and show weak haemolytic activity against human erythrocytes.Alyteserin contain at least 50% hydrophobic amino acids. Hydrophobic residues contribute to the insertion of the peptide into the hydrophobic membrane core which results in membrane disruption and death of the pathogen. Due to their mechanism of action it is less likely for resistance to develop towards such peptides compared to conventional antibiotics.</p>

<p>Influenza A NP (383-391) (HLA-B27) is a CEF control peptide that is derived from Influenza A. Influenza A is an enveloped negative-strand RNA virus that is capable of interfering with host transcription, which can ultimately cause cell death. The action of the virus particles decreases the downstream gene occupancy of RNA polymerase II, as well as instigating cellular stress, resulting in the failure of polymerase II termination at poly(A) sites. Influenza A NP (383-391) (HLA-B27) is defined as a CEF control peptide due to its antigenic properties. Clinically, this peptide is a suitable epitope for CD8+ T cells and can be used to stimulate the release of IFNg. HLA-B27 refers to the cell HLA type that this peptide acts on.The nucleoprotein (NP) is a structural protein that encapsulates the negative strand of viral RNA. NP plays a critical role in the transition of influenza virus RNA synthesis from transcription mode to replication mode.</p>

<p>Ig heavy chain V-III region Light.</p>

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

<p>Nef is an accessory protein highly conserved amongst all primate lentiviruses, it is essential for viral replication in vivo- it is expressed by human immunodeficiency virus (HIV) HIV-1 and HIV-2. Nef acts as a downregulator of class I human leukocyte antigens (HLA) expression in HIV-infected cells to help circumvent the immune response, such as cytotoxic T lymphocytes (CTL) activity. An intact nef gene is critical for high viral loads, linked to development of acquired immunodeficiency syndrome (AIDS). Certain alleles of HLA have been associated with maintaining a seronegative status such as HLA-A*1101. This nef peptide sequence (75-82) was crystallised within the class I B allele HLA B*3501 suggesting an importance of key residues required for HLA interaction resulting in a nonstandard conformational binding.</p>

<p>The native form of GLP-1 in humans is the GLP-1 (7-36) amide. GLP-1 (7-36) amide is highly unstable (half-life &lt;-2 minutes) due to proteolytic degradation by the serine protease- dipeptidyl peptidase-IV (DPP-IV). DPP-IV cleaves the N-terminal histidine and alanine residues from GLP-1 to generate two equipotent forms: GLP-1 (9-37) and GLP-1 (9-36) amide. This degradation mitigates against the therapeutic use of GLP-1 itself, therefore DPP-IV-resistant peptide analogues have been developed and licensed for clinical useThis peptide contains N-terminal 5-Carboxyfluorescein (5-FAM), a widely used green fluorescent tag</p>

<p>Epitope HLA binding for cytokine, CTL and ELISPOT assays require positive and negative controls if they are available. For SARS-CoV antigens, the HBcAg-derived H-2b-restricted peptide HBcAg (131-140) AYRPPNAPIL from the spike protein sequence is a suitable negative control.</p>

<p>The activation of transient receptor potential cation channel subfamily V member 1 (TRPV1) is believed to play a role in hyperalgesia, asthma, and hypertension. TRPV1 is important for neuronal pain detection as well as the detection of heat, capsaicin, protons, and the neurotransmitter anandamide.- The scaffold protein AKAP79 targets kinases to phosphorylate TRPV1, however it has been shown that inflammatory intermediates prostaglandin-E2 or bradykinin can activate these kinases creating a route for inflammation to cause hyperalgesia.This product is composed of the TRPV1 interacting residues of AKAP79 reordered into a scrambled sequence and conjugated to the cell penetrating TAT domain at the N-terminus. This product was shown in vivo to have a potent analgesic affect due to interaction with TRPV1 but not affect the pain threshold. This product is a vital tool for research into suitable TRPV1 antagonists.</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>Calcitonin is a peptide hormone excreted by the thyroid parafollicular cells to regulate calcium and phosphorus levels. Calcitonin acts in opposition to parathyroid hormone (PTH) and vitamin D. Calcitonin functions by inhibiting osteoclast activity in the bones preventing calcium release- there is also inhibition of renal tubular cell reabsorption of calcium and phosphate, so they are excreted preventing a rise in levels.Calcitonin is used for as marker for detection and prognosis of nodular thyroid diseases. Medullary thyroid cancer is one example of the malignant parafollicular cells detectable with the assay, as they present with an increased calcitonin level even at an early stage.Since the discovery of calcitonin over 50 years ago the salmon sourced peptide has been used in numerous treatments including bone metastases, Paget disease, hypercalcaemia, and postmenopausal osteoporosis. The salmon calcitonin has been shown to be equivalent to human form but more active and can be synthetically generated.</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>Histone H3 (1-22) 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.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.Lysine 4 of H3 (1-22) has been tri-methylated.</p>

<p>Pro-opiomelanocortin (POMC)-derived peptides act on neurons expressing the Melanocortin 4 receptor (MC4R) to reduce body weight. Setmelanotide is a highly potent MC4R agonist that leads to weight loss in diet-induced obese animals and obese individuals with complete POMC deficiency.The endogenous ligand alpha-melanocyte-stimulating hormone (alpha-MSH) for MC4R has been shown to have a much lower affinity than Setmelanotide, explaining some of the drug's potency. Administration of Setmelanotide to wildtype mice resulted in significant weight loss while  MC4R knockout mice fail to respond. Setmelanotide is in numerous clinical trials and shows promising results. Patients with POMC defects upstream of MC4R show more significant responses to treatment than those with MC4R deficiency or obese controls.</p>

<p>Histone deacetylases (HDACs) are a family of enzymes which are highly evolutionary conserved across all eukaryotes. HDACs modify histones by removing acetyl groups from the tail regions. Histone deacetylation is generally associated with reduced gene expression due to a more compact chromatin state less accessibility for transcription factors (TFs). HDACs are essential for many physiological processes including development and cellular homeostasis. They also play an important role in disease states, including neurodegenerative disorders, genetic diseases and cancers.This peptide is the fluorogenic substrate for assaying histone deacetylase (HDAC) activity in a two-step enzymatic reaction. The assay consists of the initial lysine deacetylation by HDAC followed by the release of the fluorescent group by trypsin. Fluorescence can be detected upon fluorophore release.</p>

<p>Peptide derived from the Gastric inhibitory polypeptide (GIP), an inhibiting hormone of the secretin family of hormones. While GIP is a weak inhibitor of gastric acid secretion, its main role is to stimulate insulin secretion - in a glucose-dependent mechanism. Therefore, GIP is referred to as a glucose-dependent insulinotropic peptide.GIP is derived from a 153-amino acid pro-protein encoded by the GIP gene and circulates as a biologically active 42-amino acid peptide. It is synthesised by K cells, which are found in the mucosa of the duodenum and the jejunum of the gastrointestinal tract. GIP receptors are seven-transmembrane proteins found on β-cells in the pancreas. These β-cells are those that are able to simultaneously detect glucose and release insulin as a result to GIP binding.The clinical relevance of GIP is related to type 2 diabetes mellitus (T2DM)- studies have found that T2DM diabetics are unresponsive to GIP and have lower levels of GIP secretion after a meal when compared to non-diabetics. In research involving knockout mice, it was found that absence of the GIP receptors correlates with resistance to obesity.</p>

<p>Trans-activator of transcription protein (Tat) (47-57) is a cell penetrating cationic peptide derived from the N-terminus of the Tat protein from the human immunodeficiency virus (HIV). Chimerin 1, (CHN1) is a GTPase activating protein specific for RAC GTP-binding proteins, expressed primarily in the brain. CHN1 is involved in signal transduction and is a direct effector of proteins involved in axon guidance. CHN1 is transferred to the plasma membrane and negatively regulates Rho-family small GTPases RAC1 and CDC42, to cause morphological changes to axons by pruning the ends of axon dendrites. As a cell penetrating peptide (CPP) TAT aids in the cellular uptake of molecules. TAT (47-57) can be used to deliver proteins, fluorophores, chelators and DNA to target cells.</p>

<p>An inhibitor of E2F1 and 3a transcription, with a D substituted arginine which confers resistance to proteolysis after pre-incubation in serum. Cytotoxic to several malignant cell lines and human prostate and small cell lung cancer xenografts.</p>

<p>Alpha-Casozepine (alpha-CZP) is a tryptic hydrolysate of bovine milk alphas1-casein. The presence of bile salts facilitates alpha-CZP absorption through a Caco2 monolayer. alpha-CZP shows similarities to benzodiazepines with its anxiolytic-like activity but lack the common side effects of habituation or sedation. alpha-CZP binds to the GABAA receptor at the benzodiazepine site.  alpha-CZP binds with a significantly lower affinity than benzodiazepines.Intraperitoneal administration of Alpha-Casozepine (alpha-CZP) to rodents results in anticonvulsant and sleep-protecting effects. Human administration reduces physiological stress symptoms in stressed and control patients. alpha-CZP modulated neuronal activity in brain regions linked to anxiety regulation in mice.</p>

<p>GRGD-acid is a cell adhesive peptide containing the RGD motif. This enables it the ability to increase cell adhesion and rates of cell growth, differentiation and proliferation.When immobilised onto a Poly(etheretherketone) (PEEK) surface it has been shown to increase cell adhesion and proliferation in MC3T3-E1 cells. GRGD could therefore be used in dental implants.This peptide contains a C-terminal Alexa Fluor 647 florescent dye. A cysteine residue has been added to the C-terminus for conjugation of the dye via the cysteine thiol moiety. AF647 is a bright, far-red-fluorescent dye with excitation between 594 nm and 633 nm, and is pH-insensitive over a wide molar range.</p>

<p>Dipeptide consisting of one glycine and one serine residue with diverse uses. Primary metabolite and bronsted base, forms a complex with Cu(II) acting as a tridentate ligand.Primary metabolites are metabolically or physiologically essential and are directly involved in an organism's development, growth, or reproduction.</p>