Peptides

<p>[BDP630/650]3-halphaCGRP (calcitonin gene-related peptide)</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>PDGF-Ra agonist with in vitro and in vivo antimelanoma growth activity.</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 (221-235) 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>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 (476-490) 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>The biologically active C-terminal region of human Kisspeptin. Kisspeptin, is cleaved from a 145 amino acid precursor to a 54 amino acid peptide in humans and a 52 amino acid peptide in mice. Smaller isoforms of 14, 13 and 10 amino acids have also been isolated, each sharing the common C-terminal sequence. Kisspeptin-10 (KP-10) is the most potent member of the kisspeptin family and the plasma half-life of is approximately 6 fold shorter than KP-54. KP-10 is produced by the trophoblast cells in the first trimester of pregnancy and inhibits cell migration primary trophoblasts which is essential for placental invasion.Kisspeptin, a product of the KISS1 gene, is a hypothalamic neuropeptide that stimulates gonadotropin-releasing hormone (GNRH) neurons and drives fertility. Kisspeptin binds specifically to the G-protein-coupled receptor-54, now known as Kiss1r, which is expressed in almost all GNRH neurons. Kiss1r is also expressed in other areas of the brain and periphery, highlighting other possible roles for kisspeptin outside of reproduction.</p>

<p>[β-Ala]-[Lys(AMCA)]-acid.</p>

<p>Cyclic DAG peptide targets connective tissue growth factor (CTGF/CCN2), present in the extracellular matrix, endothelial cells and overexpressed in several brain diseases. CTGF is a matricellular protein that acts as a regulator of several cellular functions, including cell adhesion, migration, mitogenesis, differentiation, and survival. CTGF is up regulated in Alzheimer's disease, Parkinson's disease, brain injury, glioblastoma, and cerebral infarction.DAG peptide has been shown to home to the brain in mouse models of glioblastoma, traumatic brain injury, and Parkinson's disease when exogenously delivered, making it an attractive target for the treatment of glioblastoma. DAG may be of use as a tool to enhance delivery of therapeutics and imaging agents to sites of brain diseases.</p>

A potent antimicrobial peptide produced by the catfish Parasilurus asotus in response to epidermal injury. Parasin I is a derivative of catfish histone H2A.

<p>LL-37, also known as CAP-18 for Cathelicidin antimicrobial peptide 18, is a 37 amino acid cationic peptide. LL-37 is also a typical linear antimicrobial peptide which can eliminate a wide range of pathogenes, including bacteria, viruses, fungi, and parasites. LL-37 is the only human cathelicidin peptide reported yet, found in lysosomes of macrophages and leukocytes.<br>LL-37 plays an important role in the first act of defense against local infection and systemic invasion of pathogens at sites of inflammation.<br>LL-37 shows cytotoxicity against bacterial and normal eukaryotic cells and is significantly resistant to proteolytic degradation. Besides its antimicrobial functions, LL-37 also has immunomodulatory roles. LL-37 suppresses the production of pro-inflammatory cytokines, TNF-α and IL-6 in infected monocytes. LL-37 increases cytokine and chemokine liberation from local cells and leucocytes and has chemotactic effects on a large number of immune cells.</p>

<p>TAT 2-4 is derived from human immunodeficiency virus (HIV) transactivator of transcription (TAT) residues 47-58. TAT (47-58) is a cell penetrating cationic peptide derived from the N-terminus of the Tat protein, which is a trans-activator of the transcription protein present in the human immunodeficiency virus (HIV). As a cell penetrating peptide (CPP) TAT aids in the cellular uptake of molecules and hence serves a valuable purpose in transduction methods. TAT 2-4 are residues (47-58) of HIV TAT protein repeated back to back, this dimer of TAT sequences has been shown to be the most efficient oligomer for cell penetration. This TAT dimer has been used in previous studies to deliver a wide variety of cargoes including fluorophores, chelators and DNA to target cells.</p>

<p>An immuno-receptor tyrosine-based activation motif (ITAM) is a phosphorylation site consisting of a conserved sequence of four amino acids that is repeated twice in the cytoplasmic tails of cell-surface non-catalytic tyrosine-phosphorylated receptors. ITAMs are involved activation of immune cells. The motif has the following structure: YxxL/I. where xx are any two amino acids. Two of these motifs are typically separated by between 6 and 8 amino acids in the cytoplasmic tail of the molecule (YxxL/Ix(6-8)YxxL/I). ITAMs are found in the CD3 and θ¶-chains of the T cell receptor (TCR) complex. TCR is a multi-subunit receptor on the surface of T cells which contains two ligand binding chains containing 20 phosphorylation sites, distributed on 10 ITAMs. The TCR θ¶-chain is a homodimer subunit that contains six ITAMs (12 sites). These sites are phosphorylated by the membrane-anchored Src family tyrosine kinase Lck and Fyn and are dephosphorylated by the transmembrane phosphatases CD148 and CD45. When both tyrosines in an ITAM are phosphorylated they generate docking sites for the tandem SH2 domains of the cytosolic tyrosine kinase ZAP-70. Bound ZAP-70 can phosphorylate tyrosines on other substrates that initiate the signal transduction that leads to T cell activation. The multiple ITAMs on the TCR function mainly to amplify subsequent signalling.T cells rely on the TCR to recognize antigens, in the form of peptides bound to major histocompatibility complexes (MHC), on the surfaces of antigen-presenting cells. Binding of TCR to antigen-MCH complexes leads to proliferation, differentiation, and the secretion of effector cytokines, contributing to the elimination of infections.</p>

<p>The full Rev is vital in aiding transport of unspliced viral mRNA from the nucleus. Within Rev there are 3 main functional regions - the arginine rich motif (ARM), the oligomerization domain (OD), and nuclear export sequence (NES). The peptide sequence 34-50 aligns to the ARM motif which binds the Rev Response Element (RRE) in RNA to form a complex which ultimately leads to nuclear export. ARM is able to recognise a wide range of RNA sequence to and still bind to form a Rev dimer. The Rev ARM sequence has also been shown to work as a nuclear localisation sequence that can penetrate cells. In research, Rev ARM has been utilised as a cell penetrating peptide (CPP) for its ability to bind RNA due to the arginine residues presenting multiple sides for binding and thus deliver macromolecules into the cell.</p>

<p>Brome mosaic virus (BMV) Gag peptide (7-25) has been utilised as a cell penetrating peptide (CPP). Translocation across the cell membrane with a cargo molecule varies in effectiveness depending on the CPP. BMV Gag (7-25) has a very high efficiency of internalisation which has been linked to the high percentage of arginine residues present.BMV Gag (7-25) 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-BMV Gag (7-25) allows a wide variety of applications particularly for conjugation, modification, and peptide design.</p>

<p>Histone 4 (H4) is one of the four core histones (H2A, H2B, H3 and H4) which are fundamental in 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's lysine rich tail plays a role in the higher order chromatin folding.</p>

<p>Peptide derived from the ubiquitin-activating enzyme 3 (UBA3), the catalytic subunit of the NEDD8-activating enzyme (NAE).</p>

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

<p>Angiotensin II (Ang-II) is a key signalling peptide of the renin angiotensin system (RAS) which is involved in regulating blood pressure, cardiovascular function and energy balance. RAS activity is elevated in obesity and is widely studied in relation to lifestyle-related diseases.Ang-II is produced from angiotensinogen (AGT) via the intermediate angiotensin I (Ang-I). AGT is cleaved by the aspartyl-protease, renin, to produce Ang-I, which is then cleaved by the dicarboxyl-peptidase angiotensin converting enzyme (ACE). ACE removes a histidine and a leucine from the C-terminus of Ang-I to form Ang-II.Ang-II exerts its affect by binding to the G-protein-coupled receptors- Ang II type 1 (AT1) and Ang II type 2 (AT2) receptors. Ang-II plays central roles in glucose metabolism and blood pressure. Increased levels of Ang-II have also been associated with Alzheimer's disease, and certain cancers including oesophageal squamous cell carcinoma (ESCC), brain cancers and breast cancers. The effects of Ang-II appear to be supressed by another branch of the RAS- the ACE2/Ang-(1-7)/Mas pathway.</p>

<p>Locustatachykinin I(LTK1 or Lom-TK-I) is a potent, rapid and persistent secretion stimulator in locust Malphigian tubules which controls primary urine production, tubule writhing and local sphincter functions.- LTK1 shares sequence homology with mammalian tachykinins such as substance P.- Two putative tachykinin receptors, Drosophila tachykinin-receptor (DTKR) and neurokinin receptor from Drosophila (NK0) have been identified.</p>

<p>Type I diabetes is an autoimmune condition caused by the destruction of insulin-producing β cells. The initiation mechanism is unclear but involves activating autoreactive T cells against the β-cell-specific antigen, insulin.RIP-B7.1 mice express CD80 on pancreatic β cells and are a model for studying de novo induction of diabetogenic CD8 T cells. Immunization of RIP-B7.1 mice with preproinsulin (ppins)-encoding plasmid DNA induces experimental autoimmune diabetes (EAD). EAD is associated with significant induction of CD8 T cells specific for the (A12-21) restricted epitope leading to the destruction of β cells.The Insulin A Chain (A12-21) epitope is recognised by pancreas-infiltrating CD8 T cells isolated from immunized, diabetic RIP-B7.1 mice as shown by flow cytometry. The Insulin A Chain (A12-21) epitope can also be used to stimulate inducible IFN- expression of ppins-primed CD8 T cells ex vivo as determined by flow cytometry. GFP fusion has shown the expression of insulin A chain (A12-21) epitope in HeLa cells.</p>