Peptidi

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.It contains 5-Carboxyfluorescein (5-FAM), a widely used green fluorescent tag.

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, peripheral, and endocrine systems. 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 G protein-coupled receptors  which 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 Galphai/o pathway. Activation of the receptor leads to a cellular influx of K+. Each receptor has been associated with neurological diseases such as GalR3 and epilepsy.Some N-terminal fragments naturally occur in vivo but their relevance is unclear. The physiological relevance of the galanin fragment (2-12) and its affinity to the various GalR receptors has yet to be made clear. Binding assays and displacement assays in rat brain tissue have been performed with similar N-terminal galanin fragments to try and elucidate their function. . The use of N-terminal fragments such as galanin (2-12) can help clarify the function of full-length galanin. This may highlight new agonists/antagonists for the galanin GalR receptors that can be putative therapeutic targets for treatments of conditions such as cardiovascular disease.NMR has used this galanin fragment (2-12) to help characterise the structure of galanin. It shows the critical residues Tyr(9), Leu(10), and Leu(11) for interaction with the galR receptors. They cluster together as collapsed hydrophobic residues irrelevant to forming higher-order structures.

The acetylated N-terminal peptide of murine myelin basic protein (MBP) (1-9).

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 (581-595) 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.

Influenza A NP (44-52) (HLA-A1) 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 (44-52) (HLA-A1) 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-A1 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.

Activation of the inflammatory response is critical to various infectious agents. Pro-inflammatory cytokines like-IL-1α and IL-1β are upregulated upon the initial detection of infection and bind to IL-1R1 to activate the signalling cascade. However, a hyperinflammatory response can lead to oxidative stress, apoptosis, and conditions such as diabetes, rheumatoid arthritis, cancer, and ischemia.To maintain homeostasis there are moderators of the inflammatory response. Binding of interleukin IL-1 to IL-1R1 stimulates the inflammatory cascade. Alternately, AF10847 binds to IL-1R1 resulting in significant conformational change of IL-1R1 but its lack of any cytokine activity locks IL-1R1 in an inactive state inhibiting a signalling event. AF10847 has an exceedingly high affinity for IL-1R1 compared to 1α and IL-1β.Extensive searches for lower molecular mass IL-1R antagonists-for oral delivery as a therapeutic for rheumatoid arthritis are being carried out. AF10847 is a 21-mer that has high affinity for the conserved IL-1R1 binding site that is also recognised by IL-1β. The remarkable high affinity of AF10847 for IL-1R1 makes it a perfect candidate for further investigations into novel IL-1R1 inhibitor development.

SARS-CoV-2 Spike (411-420)

Amylin, also known as islet amyloid polypeptide (IAPP), is a peptide hormone which is deficient in patients with diabetes mellitus (DM). Amylin is co-secreted with insulin from the pancreatic β-cells. It inhibits glucagon secretion, delays gastric emptying, and thus acts as a satiety agent.  Amylin peptide is capable of forming aggregates, and pancreatic amyloid plaques are present in 90% of patients with DM. Formation of these plaques may be inhibited by insulin via the formation of heteromolecular complexes. Amylin is also involved in adiposity signalling and body weight regulation.Amylin is expressed in the human placenta during pregnancy where it may help regulate food intake by both the mother and foetus, and is involved in foetal development of bone, kidneys and pancreas.

Apolipoprotein A-I enables the efflux of fat molecules from within cells as high-density lipoprotein (HDL) particles for transport back into LDL particles or to the liver for excretion. HDLs are one of five major groups of lipoproteins. Increasing concentrations of HDL particles are strongly associated with decreasing accumulation of atherosclerosis within the walls of arteries. Apolipoprotein A-I is often used as a biomarker for prediction of cardiovascular diseases, such that low levels of APOA1 are associated with an increased risk of adverse events in patients with coronary artery disease. In such cases, APOA1 can be used as a biomarker to predict cardiovascular disease progression.This peptide contains a covalently bonded N-terminal Biotin tag that can be used for detection and purification.

The PA protein is a subunit of the influenza virus polymerase complex and its endonuclease activity is vital in viral genome replication. As a phosphoprotein it is a casein kinase substrate and its N-terminus is responsible for the activation of a proteolytic process in which co-expressed proteins are degraded.During viral RNA synthesis PA produces 5' capped RNA oligonucleotides due to it cleaving the 5' terminus on pre-mRNA. It is possible that the PA protein could be used as a target in antiviral chemotherapy.

Thrombin receptor inhibitory peptide (TRIP). Thrombin activates members of the PAR family of receptors to initiate a variety of signalling pathways.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. This peptide mimics the tethered peptide ligand of PAR- 2, but lacks the S42 residue which is important for receptor activation, and therefore acts as a thrombin antagonist peptide.

Recombinant human interferon-β (IFNB) is a therapeutic for specific stages of multiple sclerosis (MS). However, a significant portion of patients develop neutralising antibodies within two years which prevent the clinical efficacy of the treatment- this was correlated to a specific rise in IgG. Sequencing of IFNB1 revealed CD4+ T cell epitope residues (118-132) that contain critical T cell activation residues. Identifying these sequences allows them to be manipulated to provide new interferon treatments that reduce the capacity to induce neutralising antibodies in MS patients. In addition, the critical residue isoleucine has been mutated to valine and shown to reduce the immunological response to this epitope. This IFNB1 (118-132) epitope can be used for immunological investigations as a deimmunised version of the epitope. In addition, it can be used as a control for T cell activation and antibody recognition via immunoassays and immunohistochemistry. This may provide further insights into specific haplotypes correlating to IFNB responses in MS treatment.

Boc-Val-Pro-ValP(OPh)2 is a good inhibitor for HLE (Human Leukocyte Elastase) and porcine pancreatic elastase (PPE).

Buforin II is a highly potent antimicrobial peptide which was derived from buforin I, a peptide isolated from the stomach of the Asian toad, Bufo bufo garagrizans. Buforin II is an alpha-helical antimicrobial peptide, however it has far stronger antimicrobial activity against a broad spectrum of microorganisms compared with other alpha-helical antimicrobial peptides. Buforin II may have a different mode of action to that of other alpha-helical peptides targeting nucleic acids instead of cell membranes.

Biotin-Tat (47-57) 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). Specifically Biotin-TAT (47-57) is located within the arginine-rich basic domain 48-60 of the TAT peptide which as a whole has three domains which function to aid HIV through transactivation, DNA binding and nuclear transport. As a cell penetrating peptide (CPP) TAT aids in the cellular uptake of molecules and hence serves a valuable purpose in transduction methods. This property has been demonstrated through its ability of allowing toxins such as the neurotoxin Botulinum neurotoxin Type A, produced by the Clostridium botulinum type A bacteria to penetrate the skin barrier non-invasively.This peptide has an uncharged C-terminal amide.

SARS-CoV-2 NSP13 (336-350)

H-STMSIT-OH peptide, corresponding to RNase A 77-82 (Chain A of bovine pancreatic ribonuclease) has been published to have amyloidogenic properties, and under certain conditions H-STMSIT-OH hexapeptide forms amyloid fibrils. Please also see CRB1001321, which you can use as a negative control in amyloid formation experiments.

Myocarditis is an inflammatory heart disease often associated with a previous viral infection. Evidence has suggested that myocarditis may be due to autoimmune responses directed against cardiac tissue. The inflammatory immune response caused after infection may break tolerance by mechanisms of molecular mimicry, bystander activation, and loss of immune regulation. Experimental autoimmune myocarditis (EAM) is a model of inflammatory heart disease generated by immunizing susceptible rats or mice with cardiac myosin or its myocarditic epitopes. In the EAM model, cellular infiltrates consist primarily of T cells and macrophages, and T lymphocytes responsive to cardiac myosin can transfer disease. Cardiac myosin is a large peptide, which is composed of two H chains and two pairs of L chains. Proteolysis of myosin yields three subfragments including a globular head or subfragment 1 (S1) region, an alpha helical coiled coil rod comprised of subfragment 2 (S2), and light meromyosin (LMM). In the Lewis rat, the S2 subfragment has been shown to produce the most severe myocarditis.