Peptides

SCO-spondin is a large multi-domain glycoprotein of the extracellular matrix, widely distributed in the central nervous system (CNS). SCO-spondin is expressed and secreted in early development by the subcommissural organ (SCO), an ependymal differentiation of the brain. SCO-spondin is part of the Reissner's fiber (RF), a thread-like structure in the spinal cord and is involved in axonal pathfinding, development of brain commissural fibres and spinal cord regeneration in vertebrates. SCO-spondin also interferes with several developmental processes including: neuronal development- axonal pathfinding- neuronal survival- neurite extension- neuronal aggregation, and fasciculation.SCO-spondin has several conserved domains, including 26 thrombospondin type 1 repeats (TSR), nine low-density lipoprotein receptor (LDLr) type A domains, two epidermal growth factor (EGF)-like domains, and N- and C-terminal von Willebrand factor (vWF) cysteine-rich domains. The TSR motifs are highly important in many of SCO-spondins neuronal responses.NX210 corresponds to part of the SCO-spondin TSR sequence, it can increase adhesivity and neuritic outgrowth and is involved in cell-cell and cell-matrix interactions. NX210 can increase cell survival and induce neurite outgrowth.

Thrombin is the main effector of the coagulation cascade- it is a serine protease. Thrombin binds to active protease activated receptor (PAR) which belongs to a subfamily of G-protein coupled receptors (GPCR). Thrombin activation of mouse PAR-4 reveals an amino terminus sequence of GYPGKF. This is the natural ligand for PAR-4. GYPGKF binds internally to the receptor and leads to signalling activation. Identification of GYPGKF as a PAR-4 agonist has allowed better understand of the function of PAR. Addition of GYPGKF to PAR-4 expressing cell lines achieved 55% of the maximal response of thrombin. GYPGKF can provide understanding of PAR-4 and a template for more potent agonists.

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.Acetyl-Histone H4 (1-21)-has an uncharged C-terminal amide and is protected from N-terminal modifications by a covalently bonded acetyl group.

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.

SMAC/DIABLO [Lys(5-FAM)] is a pro-apoptotic peptide that is derived from the mitochondrial protein known either as Second Mitochondria-Derived Activator of Caspases (Smac) or Direct IAP Binding Protein with low isoelectric point, pI (DIABLO). During apoptosis the mitochondria has increased permeability to Smac/DIABLO, which causes the protein to diffuse into the cytosol. Here, Smac/DIABLO adheres to Inhibitors of apoptosis proteins (IAPs) and prevents them from binding to caspases, which in turn accentuates apoptosis.This peptide has a C-terminal lysine linker labelled with 5-Carboxyfluorescein (5-FAM), a widely used, green fluorescent tag.

A Chemerin-9 peptide derived from chemerin, a protein that is involved in a variety of functions such as autocrine, angiogenic, reproductive and chemotactic processes. Chemerin-9 binds to the chemerin receptor 23 (G-protein coupled receptor) and causes the receptors internalisation.

Ara h 2 is one of the major allergenic proteins from peanut (Arachis hypogaea) which contains approximately 13 potential allergenic proteins.Ara h 2 is a member of the 2S albumins (conglutinins) belonging to the prolamin superfamily which also includes Ara h 6. 2S albumins contain major food allergens from seeds of many mono- and dicotyledon plants and share a common compact structure that renders the proteins highly resistant to proteolysis.In mouse models Ara h 2 and Ara h 6 are the main cause of effector responses such as mast cell degranulation and anaphylaxis. Ara h 2 has a high predictive value for diagnosis of clinical peanut allergy and is also more potent than Ara h 1 or Ara h 3 in histamine release assays and skin prick tests.This peptide represents a tryptic peptide of Ara h 2.

ANP (13-26) 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 the cardiovascular remodelling process.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 proANP (1-126) which is converted into the circulating forms by the type II transmembrane serine protease Corin.

KR-12-a5 (6-DL).

Aβ has been identified as the key subunit of the extracellular plaques found in the brains of patients with Alzheimer disease (AD) and Down syndrome (DS). Aβ has therefore been extensively studied as a potential target for treatment of AD.Aβ is formed from the cleavage of the large, transmembrane protein- APP (amyloid precursor protein). Cleavage of APP by β- and then &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.

Numerous studies have found BMAP-28 to have AMP activity against various bacteria, fungi, and some parasites such as Leishmania. Of note, studies show it inhibits multi-drug resistant (pan-resistant) species of both Gram-negative and Gram-positive bacteria including Acinetobacter baumanniim, Pasteurella multocida, and MRSA. With the rise in antibiotic-resistant species, BMAP-28 is a useful discovery for creating new more potent analogues.In mammalian studies BMAP-28 induces cancer cell death and prevents growth, via inducing mitochondrial pore opening and depolarisation leading to cell apoptosis making it a target for future cancer treatment.

Herceptide

Substrate for the severe acute respiratory syndrome coronavirus main protease (SARS-CoV Mpro). The substrate sequence is derived from residues P4-P5' of the SARS-CoV Mpro N-terminal autoprocessing site and was identified by a docking study. This substrate binds to and acts as a competitive inhibitor of SARS-CoV Mpro, (3CLpro).Experiments show that the octapeptide AVLQSGFR is bound to SARS-CoV Mpro through six hydrogen bonds. It is an effective inhibitor of SARS coronavirus with an EC50 of 2.7 x 10-2 mg/L and is able to block replication of the virus. The octapeptide also shows no detectable toxicity in the host cells.

Glucagon like-peptide-2 (GLP-2) is a gut hormone produced in the enteroendocrine L cells of gastrointestinal tract by the cleavage of the 160-amino-acid proglucagon molecule. GLP-2 is secreted following the ingestion of food and carries out its activities via the GLP-2 G-protein coupled receptors (GLP-2Rs). GLP-2 has a range of roles within the cell, including: anti-inflammatory effects promoting the expansion of the intestinal mucosa, stimulating intestinal blood flow, inhibiting gastric acid secretion and gastric emptying, increasing intestinal barrier function and enhancing nutrient and fluid absorption.

Pep-1 is a synthetic cell-penetrating peptide (CPP), and has been successfully used to deliver a variety of proteins and other biopharmaceutical macromolecules into cells in a non-disruptive manner. It is a CPP with primary amphipathicity, which results from its amino acid sequence as opposed to its folding structure. The primary structure of Pep-1: Chariot comprises three main domains: a tryptophan-rich, hydrophobic domain, and a hydrophilic domain derived from an NLS (nuclear localisation signal) of SV40 (simian virus 40) large T-antigen, and a spacer.

Fibrinogen (377-395) Human is derived from Fibrinogen, which is a large plasma glycoprotein with a complex structure, and one of the most abundant proteins in blood. Fibrinogen is important in fibrin clot formation, haemostasis, and inflammatory responses. Increased plasma fibrinogen indicates a proinflammatory state and is a risk factor for vascular inflammatory diseases including hypertension and atherosclerosis. Fibrinogen cleavage products act as inflammatory activators in the pathophysiology of allergic asthma.Fibrinogen (377-395) Human is capable of preventing microglia activation by inhibiting the Mac-1 receptor, which in turn suppresses relapsing paralysis.

TP10 is an amphipathic cell-penetrating peptide (CPPs) also known as transportan 10. Its formation involves the use of a lysine residue to form a chimeric linkage between a mastoparan 21-residue peptide, a wasp venon 14-residue peptide and 6-residues derived from the neuropeptide galanin. Structurally TP10 contains only positively charged amino acids along with 4 lysines and an N-terminus. Therefore it will produce a +5 charge under conditions of a neutral pH. It has been found that TP10 may aid molecules in penetrating through the cell membrane barrier through directly interacting with the lipid bilayer. During these interactions with the membrane TP10 will form an amphipathic alpha-helix. TP10 can be used in transduction methods.

The Influenza Virus Nucleoprotein (311 - 325) is a component of the viral ribonucleotide complex, derived from the influenza virus and it is involved in viral replication, RNA packing and nuclear trafficking. As a monomer it contains basic residues which allow it to bind to single stranded RNA and through its flexible tail loop it has the ability to form NP oligomers.Furthermore NP is able to support the viral polymerase structurally, through associating with the two subunits PB1 and PB2, and it allows the viral ribonucleotide complex to be transported in and out of the nucleus due to its nuclear localisation and nuclear export signals.During influenza viral replication messenger RNA, viral genome RNA and complementary positive-sense RNA are produced and NP is crucial for this replication.Inhibitors of NP have potential to be used to prevent the influenza virus in humans.

HPV16 E6 pep11**m.

PDGF-Ra agonist with in vitro and in vivo antimelanoma growth activity.

[β-Ala]-[Lys(AMCA)]-acid.

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.

Histone H3 (10-29)-Biotin is derived from Histone 3 (H3) which is one of the four core histones (H2A, H2B, H3 and H4) fundamental in compacting eukaryotic DNA into the nucleosome. The nucleosome arises when 147 base pairs of DNA wrap around a H3-H4 tetramer and two H2A-H2B dimers, forming the histone octamer core. Both H4 and H3 are highly conserved and perform roles in binding to segments of DNA which enter and leave the nucleosome and in chromatin formation. Similar to the other core histone, H3 has a globular domain and a flexible N-terminal domain, 'histone tail' which can undergo modifications such as acetylation, methylation, phosphorylation and ubiquitination. Due to histones containing a large number of lysine and arginine residues they have a positive net charge which interacts in an electrostatic manner with the negatively charged phosphate groups in DNA. The transcriptional activation or silencing of the chromatin is controlled by ATP-dependent chromatin remodelling factors and histone modifying enzymes which target histone proteins. Both processes function to alter the positioning of the nucleosome, allowing the DNA it to be either available or inaccessible to the transcription machinery.Another modification process histones can undergo is biotinylation where the covalent attachment of a biotin molecule is catalysed by the enzyme Biotinidase. This cleaves biocytin to generate a biotinyl-thiester intermediate. The biotinyl can then be transferred onto the histone lysine ɛ-amino group which 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.

Cell penetrating peptides (CPP) can transport molecules such as nucleic acids, proteins, and imaging agents into cells of interest. Pas PR9, nona-arginine, is an arginine rich CPP. It is composed of the nona-arginine: R9 and Pas which is a peptide penetrating accelerating sequence (PAS) and it functions to export molecules out of endocytic vesicles. During a study in which PR9 was in complex with a Quantum dot probe (QD) it was evident that the PR9/QD complex was transported into the cell through endocytosis and co-localises with actins, lysosomes, early endosomes and the nucleus. Due to the non-toxicity of the PR9/QD complex it can be used as a safe vector for biomedical purposes.PR9 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- PR9 allows a wide variety of applications particularly for conjugation, modification, and peptide design.

Histone H3 (1-21) K4ac is derived from Histone 3 (H3) which is one of the four core histones (H2A, H2B, H3 and H4) fundamental in compacting eukaryotic DNA into the nucleosome. The nucleosome arises when 147 base pairs of DNA wrap around a H3-H4 tetramer and two H2A-H2B dimers, forming the histone octamer core. Both H4 and H3 are highly conserved and perform roles in binding to segments of DNA which enter and leave the nucleosome and in chromatin formation. Similar to the other core histone, H3 has a globular domain and a flexible N-terminal domain, 'histone tail' which can undergo modifications such as acetylation, methylation, phosphorylation and ubiquitination. Due to histones containing a large number of lysine and arginine residues they have a positive net charge which interacts in an electrostatic manner with the negatively charged phosphate groups in DNA. The transcriptional activation or silencing of the chromatin is controlled by ATP-dependent chromatin remodelling factors and histone modifying enzymes which target histone proteins. Both processes function to alter to change the positioning of the nucleosome, allowing the DNA it to be either available to the transcription machinery or inaccessible.The Histone H3 (1-21) lysine 4 has been acetylated.

Jelleines are a family of very small (8-9 amino acid residues long) host defence peptides (HDPs) isolated from the royal jelly of honey bees (Apis mellifera). Jelleines do not present any similarity with other HDPs from other honeybees and are produced by the workers and secreted into Royal Jelly and provide abroad-spectrum protection of the bee hive against microbial infections. The Jelleines are not considered cytolytic or directly involved with inflammatory effects.Possess antimicrobial properties against yeast, fungi, gram-positive and gram-negative bacteria.PLEASE NOTE that in several published articles the sequence of Jelleine-3 has been printed as EPFKISLHL-NH2, due to a mistake in the original reference: Fontana et al., (2004). The correct sequence, is EPFKISIHL-NH2.

Leuprolide acetate is a synthetic peptide analogue of naturally occurring gonadotropin releasing hormone (GnRH also known as luteinising hormone-releasing hormone, LHRH). Leuprolide Acetate has a longer half-life and a higher affinity to the pituitary GnRH-receptor than physiological GnRH due to the presence of a D-amino acid. Leuprolide acts as a super-agonist of the pituitary gonadotropin-releasing hormone (GnRH) receptor in the hypothalamo-pituitary-gonadal axis and disrupts the maintenance of the normal hypothalamo-pituitary-gonadal axis and desensitizes the GnRH receptor. This results in lower levels of testosterone in the blood. Leuprolide is used to treat prostate cancer, endometriosis, fibroids and precocious puberty. Peptide is for research purposes only, strictly not for human use.

GIP (1-30) Human amide is derived from the Gastric inhibitory peptide (GIP). Gastric inhibitory polypeptide (GIP) is 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. 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.

Pantinin-1 is an antimicrobial peptide (AMP) identified from the venom of the scorpion Pandinus imperator. Pantinin-1 possess strong antimicrobial activity against Gram-positive bacteria and fungus, and weak activity against Gram-negative bacteria, with very low haemolytic activities against human red blood cells.

Apoptosis can be triggered by permeabilization of the mitochondrial membrane leading to leakage of cytochrome c. Work shows this mitochondrial pathway to apoptosis involves pro-apoptotic proteins of the Bcl-2 family including Bak that directly permeabilise the mitochondrial membrane leading to leakage and catastrophic cell damage. The activities of apoptotic proteins are held in check by antiapoptotic paralogs, including Bcl-2. The interactions between these proteins are modulated by BH3-only proteins. BH3 proteins have 9 -15 amino acid BH3 domain and act as direct activators or sensitizers of pro-apoptotic proteins including Bak. PUMA has been identified as a BH3 protein, but its role is less clear. PUMA BH3 peptide provided here is the full 15 residue domain shown to act as a direct activator of Bak activity leading to caspase activity and apoptosis. A direct interaction with Bak has been demonstrated by surface plasmon resonance analysis. Critical data of PUMA and Bak regulation has not been well established. Further work with this peptide may help to clarify the function and role of the PUMA BH3 domain as a direct Bak activator.