Peptídeos

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.

Fibrinogen b43-63 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.The conversion of monomeric fibrinogen into polymeric fibrin is mediated by thrombin, which binds to fibrinogen and catalyses cleavage of fibrinopeptide A (FpA) and fibrinopeptide B (FpB). Fibrinopeptide B is protected from modifications such as carbamylation by pyroglutamination of the N-terminal amino acid.

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.

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.

Indolicidin is a natural cationic cathelicidin family anti-microbial peptide (AMP) with a very wide killing spectrum which includes: Gram-positive and Gram-negative bacteria, fungi, protozoa and HIV.  It is also an immune system modulator and an inhibitor of aminoglycoside antibiotic-resistance enzymes.Indolicidin contains 5 tryptophan residues (39% of peptide content)- the highest tryptophan proportion ever seen in a peptide or protein.When indolicidin interacts with biological membranes it assumes a wedge- shaped conformation, with the hydrophobic tryptophan residues in the trough of the wedge, and positively charged regions flanking them at each end. If fully extended, indolicidin is able to span both lipid bilayers despite only consisting of 13 amino acid residues. This is possible because indolicidin adopts an approximate poly-l-proline type II helix conformation, which is characterized by very high helical pitches.The exact mode of action of indolicidin is still unknown. At bactericidal concentrations the peptide appears to translocate through the membrane into the cytosol where it may bind to nucleic acids, whereas at higher concentrations it is membranolytic.

Peptide identified through phage display that binds to colorectal cancer cell line RKO cells, as well as other cancer cells including Caco-2, HCT 116 and HCT-15, but not to normal cells, possibly through targeting the monocarboxylate transporter 1, which has been implicated in colorectal cancer progression and prognosis.

This peptide contains an N-terminal a 5-carboxytetramethylrhodamine (5-TAMRA), a widely used fluorescent dye which excites at 546 nm and emits at 579 nm and a black hole quencher 2 (BHQ-2) group.The fluorescence from 5-TAMRA is efficiently quenched by resonance energy transfer to the BHQ-2 group when the peptide is intact, however upon cleavage of the peptide by Mpro, 5-TAMRA and BHQ-2 are separated, allowing fluorescence to be detected. This therefore represents a useful tool for investigating Mpro activity.

C- terminal fragment of adrenocorticotropic hormone (ACTH) also known as corticotropin, and competitive antagonist of ACTH receptor (ACTHR), also known as melanocortin type 2 receptor (MC2R).ACTH is a member of the melanocortins-peptide family, this tropic hormone is produced and secreted by the anterior pituitary gland. ACTH is an important component of the hypothalamic-pituitary-adrenal (HPA) axis and is often produced in response to biological stress. ACTH acts to increase the production and release of cortisol via its interaction with ACTHR. Receptor activation increases the intracellular concentration of cAMP via adenylyl cyclase. Abnormal ACTH levels in the body have been linked to primary adrenal insufficiency/Addison's disease, Cushing's disease and secondary adrenal insufficiency.

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).

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.

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.

Ig heavy chain V-III region Light.

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

The rise of antibiotic resistance has led to the search for new drug alternatives. Antimicrobial peptides (AMPs) have been identified as a lucrative area for molecule design. The polar fish Pleuronectes americanus expresses polyalanine peptide (pALA) which has been shown to be an AMP against biofilms, and gram-negative bacteria, while not being toxic to mammalian cells. pALA forms an alpha helical conformation that is effective at permeabilising the gram-negative bacteria membrane inducing fatal cell leakage. pALA provides a suitable model for molecule design to hopefully provide new drugs as we enter the post-antibiotic era.

BNP-32, porcine is an N-terminal six amino acid extended form of BNP and henceforth is designated BNP-32. BNP and BNP-32 are found to be the major forms of BNP family in porcine brain.BNP-32 is a cardiac neurohormone and is secreted from the myoendocrine cells of the ventricles of the heart in response to volume expansion and pressure overload it has natriuretic, vasodilatory and cardiovascular homeostatic effects and suppresses the renin-angiotensin-aldosterone system.

Secretoneurin (SN) is a sensory neuropeptide derived from secretogranin-II by cleavage. SN is conserved from sharks to mammals, work with models suggests it has diverse and important roles. Use of mouse models suggests SN binds to secretoneurin G protein coupled receptors (GPCRs). SN binding stimulates dopamine release from striatal neurons and monocyte migration. SN potently recruits eosinophils in the lungs. Interestingly, in models SN stimulates pituitary luteinizing hormone release.With an array of actions as diverse as that seen with other sensory neuropeptides, there are also numerous inflammatory conditions linked with SN. As mentioned earlier, SN recruits eosinophils in the lungs and thus is being studied for a role in asthma. Study of autoimmune encephalomyelitis suggests SN may be recruited to the inflammatory lesion on the central nervous system. Further evidence to an inflammatory role, SN levels are downregulated in rheumatoid joints, but the relevance has yet to be established. Significant changes are noted in certain forms of dementia and Alzheimer. Many aspects still require work, but SN has the potential to reveal underlying mechanisms of these inflammatory conditions and new therapies.

Portion of EBV EBNA 3A

Peptide derived from the HIV transactivator of transcription protein. TAT is a cationic cell-penetrating peptide.