Peptídeos

Duchenne muscular dystrophy is a severe muscle wasting X-linked genetic disease cause by mutations in the gene encoding the muscle structural protein, dystrophin. Exon skipping therapy remains a key approach for treatment of DMD but still requires considerable research to improve efficient and specific delivery of molecules to myofibers. Use of a phage library identified this sequence as having a high affinity for myofibers. Conjugation of this peptide to novel DMD molecules could provide the insights needed in the field.

LHRH.

RAGE antagonist peptide is an S100P-derived peptide based competitive antagonist for receptor for advanced glycation end product (RAGE). Recent studies have shown it to disrupt the interaction between RAGE and its ligands, such as S100P, S100A4 and HMGB-1 in binding assays and in multiple cancer cell lines. As well as this, it also blocks RAGE-dependent NF-kB activation in MPanc96, MOH and HPAF II tumor cell lines.Systemic administration of RAGE antagonist peptide also diminishes NF-kB signaling in vivo and significantly reduces glioma tumour growth in murine models.

IRBP (1-20) is derived from the interphotoreceptor retinoid-binding protein (IRBP), present in the interphotoreceptor matrix and is expressed by cone and rod photoreceptors in the eye. IRBP is involved in retinoid delivery and protects retinal cells from oxidative stress.In retinitis pigmentosa patients, IRBP can be subjected to mutations resulting in a non-secreted form of IRBP to be produced. Furthermore IRBP gene mutations have been associated with high myopia and retinal dystrophy.The expression of IRBP is reduced in diabetes patients which may lead to visual cycle misfunction and the photoreceptors can be vulnerable to damage.

TP10 is an amphipathic cell-penetrating peptide (CPP) 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 α-helix. TP10 can be used in transduction methods.TP10 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-TP10 allows a wide variety of applications particularly for conjugation, modification, and peptide design. Fluorescent labelling of TP10 for drug delivery has been used in vivo.

Membrane-active peptide that binds to HDM-2 expressed in the membranes of solid tissue tumour cells to induce transmembrane pore formation in cancerous, but not normal cells, resulting in tumour cell necrosis independent of p53 activity.

LL-37 is a member of the large cationic family of anti-microbial peptides called cathelicidins which have broad-spectrum anti-microbial activity and are expressed in many species. The only cathelicidin found in humans is LL-37, this is produced in epithelial cells, by proteolytic cleavage from the C-terminal of the hCAP-18 protein. LL-37 can be processed into different forms of anti-microbial peptides. As well as its anti-microbial properties LL-37 also regulates many aspects of the innate immune system and overexpression of LL-37 has been linked to autoimmune diseases such as asthma and psoriasis, making LL-37 the most studied form of the human cathelicidin peptides.More recently, studies have shown that LL-37 binds to SARS-CoV-2 S protein and inhibits binding to its receptor hACE2, which may inhibit viral entry into the cell. LL-37 is upregulated by vitamin D, therefore this may be one mode of action for the positive outcomes seen with vitamin D treatment for Covid-19.

Vasoactive intestinal peptide (VIP) is a neuropeptide found throughout the body and the central nervous system (CNS). VIP is located within cell bodies and nerve endings of the enteric nervous system, brain and pancreas. VIP neurons in the peripheral system fire to regulate blood vessels, and the  CNS innervate cerebral vasculature. VIP  binds to G protein-coupled receptors VPAC1 and VPAC2. VIP and VPAC2 are detected in circular smooth muscle cells of cerebral arterioles. VIP and VPAC1 are also found in lymphatic tissue. VIP can block inflammation, modify the Th response favouring Th2 and induce regulatory T cells. Overexpression of each receptor has been linked to various cancers.VIP administration leads to pancreatic bicarbonate-rich fluid secretion but not to the same degree stimulated by secretin. VIP stimulates insulin secretion in a glucose-dependent manner and also stimulates glucagon secretion. Studies have found that in morbidly obese patients, VIP levels are lowered and work to slow gastric and duodenal motility but increase gastric emptying. Therefore, decreasing VIP levels in obese patients may increase weight gain by accelerating gastric emptying.VIP has been well studied in pancreatic acini. VIP is a full agonist of amylase secretion and increases cyclic AMP synchronised with an increase in intracellular Ca2+ triggered by stimuli that act through cholecystokinin (CCK) or cholinergic agonists. Most cAMP increases, and amylase secretion appear to be mediated via VPAC1.The discovery of VPAC antagonists can help to understand VIPs roles and may also provide new therapies in VIP dysregulated systems such as cancers. VIP (6-28) is a specific competitive inhibitor of the VIP receptor derived from VIP. VIP-induced vasodilatation was blocked by co-administration of the VIP receptor antagonist VIP (6-28). Using a VIP receptor antagonist has made VIP function easier to study during neuronal injury, inflammation, and heart innervation. The VIP receptor antagonist is being considered for osteoarthritis treatment, an area with no current treatments other than analgesics.

TatCN21 is an inhibitor peptide for the calcium/calmodulin-dependent protein kinase II (CaMKII), a ubiquitously-expressed multifunctional serine/threonine protein kinase. TatCN21 blocks both autonomous and stimulated CaMKII activity with high selectivity. CaMKII is highly expressed in brain tissue where it regulates several processes including: neurotransmitter synthesis/release, neuronal plasticity- excitability and calcium homeostasis. Glutamate clearance by astrocytes is an essential part of normal excitatory neurotransmission, and accumulation of glutamate in the central nervous system is associated with many neurodegenerative disorders. CaMKII regulates glutamate homeostasis: CaMKII inhibition results in diminished glutamate uptake, dysregulated calcium homeostasis, release of the gliotransmitter ATP and compromise neuronal survival. Loss of CaMKII signalling may be an important factor in excitotoxicity. Peptide was obtained by linking the 11 amino acid human HIV Tat transporter to a 21 amino acid sequence corresponding to the CN21.

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. The scrambled peptide was shown in vivo to have no effect on TRPV1 algesia and thus is a vital control for research work. This product is a vital tool for research into suitable TRPV1 antagonists. The scrambled-TAT peptide is available for purchase in both an acid and amide form, this is the C-terminal amide form.

With the rise of multidrug-resistant bacteria like P. aeruginosa, the hunt for low toxicity inhibitors is paramount. A crucial part of their virulence/life cycle is cleavage of signal peptides. Type I signal peptides have a C-terminal hydrophilic domain containing a signal peptidase cleavage site commonly found in P. aeruginosa proteins that are cleaved by type I signal petidases (SPases). P. aeruginosa LasB, a type I signal peptide, is a crucial enzyme for bacterial invasion, it degrades elastin and thus aids tissue invasion, without cleavage by a SPase the protein is inactive. This peptide is an ideal candidate for enzymatic assay work in to SPase inhibitor investigations.Here we provide the substrate LasB sequence with the EDANS-Dabcyl donor quencher pair suitable for SPase inhibitor assays with FRET microscopy analysis. When this peptide is intact, fluorescence from the fluorophore (donor) EDAN is undetectable due to the proximity of the acceptor (quencher) Dabcyl. However, upon cleavage the fluorescence of the EDANS moiety, as measurably by excitation/emission 340/490nm, can be detected due to separation from the Dabcyl quencher.

Melittin is a 26-residue peptide originally isolated from venom of the European honeybee. Melittin is a cationic, hemolytic peptide from honey bee venom. Melittin lowers the surface tension at the plasma membrane and causes cell lysis. Melittin exhibits potent anti-inflammatory and antimicrobial activity. Melittin has been extensively used as a model peptide for observing membrane lipid-protein interactions.

β-Amyloid 1-10 (Aβ1-10) is one of many short Aβ species found in vivo and is formed by the cleavage of amyloid β precursor protein by β- and α-secretase.-Amyloid β-protein (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 α-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. Biotin is C-terminally linked to the peptide via ethylenediamine-for convenient detection and purification. Alternative β-Amyloid fragments and labels are also available, please refer to our peptide catalogue for availability.

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.

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 <-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 use. Contains an N-terminal biotin tag for easy detection and purification.

Keratin-Derived anti-microbial Peptides (KDAMPs), are peptide fragment of the intermediate filament protein cytokeratin 6A. They were originally isolated from lysates of human corneal epithelial cells. KDAMPs exhibit coil structures with low α-helical content and are smaller and more stable than other known host-expressed anti-microbials.Multiple length KDAMPs have been studied for their anti-microbial properties, and different fragments show different anti-microbial spectrums. The 19 mer KDAMP peptide is rapidly bactericidal against multiple clinical isolates of Pseudomonas aeruginosa, and shows even greater activity against-Streptococcus pyogenes. However it is not active against Staphylococcus aureus-or-Escherichia coli.