Peptídeos

CooP peptide specifically homes to invasive tumours such as glioblastoma and their blood vessels. Mammary-derived growth inhibitor (MDGI), also known as the fatty-acid binding protein 3 (FABP3) or the heart fatty acid-binding protein (H-FABP) is the binding partner for the CooP peptide. Coop peptide homes to all tumours which express MDGI and their associated vasculature. MDGI is not however expressed in the normal human brain. Therefore the CooP peptide appears to have a highly selective specificity as a homing peptide and the potential to deliver targeted therapy to treat invasive brain tumours.CooP peptide has been successfully used for the targeted delivery of chemotherapy and different nanoparticles.

Portion of HCMV

HIV-1 replication is rapid and error prone which is beneficial to the virus as it allows mutations to arise that aid evasion of the host immune system and resistance to drug treatment. RT is the key target for most anti-HIV drugs and therefore conserved sequences are useful to aid further research into new less toxic antiviral treatments.  HIV-1 reverse transcriptase (RT) converts the RNA genome into DNA during retroviral replication. HIV-1 RT is a heterodimer composed of 2 subunits, p66 and p51. HIV-1 RT heterodimer has 2 enzymatic functions, DNA polymerase and Rnase H resulting in nucleic acid translation to a linear DNA duplex. Complete inhibition of viral replication is the only known method of preventing HIV-1 drug resistance and disease progression.HIV RT epitopes have become a useful research tool as an in vitro antigenic challenge to study cytotoxic T lymphocyte (CTL) responses to retroviruses. The HIV-1 RT A2-YI9 sequence has been shown to be an effective epitope for CTL recognition leading to lysis of HIV-infected T cells. The A2-YI9 is also considered a potential for vaccine development due to it being a well conserved sequence.

Neuropeptide and hormone involved in many processes, including- social bonding--sexual reproduction- childbirth and breastfeeding. Oxytocin is synthesised in the hypothalamus as a prepropeptide consisting of a signal peptide, the oxytocin peptide hormone, a processing signal and the carrier protein- neurophysin. The prohormone then undergoes endoproteolytic cleavage and amidation to form the final oxytocin peptide.Dysregulation of oxytocin has been implicated in the pathophysiology of neuropsychiatric disorders that impact social functioning, such as autism, schizophrenia, and depression as well as anorexia nervosa. Intranasal oxytocin administration may reduce amygdala activity and amygdala-midbrain connectivity in response to fearful situations- reduce cortisol release and anxiety in response to psychosocial stress- increase trust behaviour- increase the ability to interpret mental states, and increase the amount of time spent gazing at the eyes when viewing faces.

Candidate peptide substrate for kallikrein-related peptidase 5 (KLK5). In its intact state this peptide is not fluorescent, however when this substrate peptide is cleaved, Rhodamine 110 is released and thus fluorescence can then be detected. Contains rhodamine 110 group, a widely used red fluorescent tag. The terminal carboxylic acids in this peptide have been activated by the addition of the p-tosyl moiety, allowing for easy addition of functional groups or further peptide residues.

Residues 1-12 of the gastrointestinal hormone motilin, secreted from endocrine cells in the small intestines, mainly from the jejunum and duodenum, in response to the fasting, drinking water or the mechanical stimulus of eating.

RAG8 is a pepducin- a cell-penetrating palmitoylated peptide with a C-terminal NH2.- Palmitoyl is a 16-carbon aliphatic chain which enhances the hydrophobicity of the peptide, and therefore improves its penetration through lipid structures.The peptide sequence corresponds to a key regulatory sequence at the intracellular C-terminus of PAR4. This motif regulates calcium signalling and PAR4 interactions with the signalling protein-β-arrestin. RAG8 is a PAR4 antagonist that can attenuate calcium signalling and β-arrestin-1 and 2 recruitment to PAR4 which has been activated with the PAR4 agonist AYPGKF-NH2.Disrupting this PAR4/β-arrestin signalling pathway with RAG8 blocks PAR4 dependent platelet activation and reduces stability of blood clots.

Histone H3 (1-20) K4Me2 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. 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. Like 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 many lysine and arginine residues, they have a positive net charge which interacts electrostatically 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 change the positioning of the nucleosome, allowing the DNA to be either available to the transcription machinery or inaccessible.Histone tails can undergo multiple modifications, including acetylation, methylation, ubiquitylation and sumoylation.  The modification pattern is believed to alter chromatin function/structure. Histone H3 (1-20) K4Me2-GG-[Lys(5-FAM)] lysine 4 has been dimethylated, has a C-terminal GGK linker labelled with 5-Carboxyfluorescein (5-FAM), a widely used green fluorescent tag. This peptide also has an uncharged C-terminal amide. H3 (1-20) K4Me2 has been investigated to understand its effect on epigenetic regulation through NMR with histone readers such as zinc finger domains. Histone H3 (1-20) K4Me2-GG-[Lys(5-FAM)] can be used to study the function of this pattern on chromatin availability and histone effectors via crystallisation, pull-down assays and protein blots.

VP4 is a viral coat protein of Nora virus encoded for by ORF4. The product of these gene is likely cleaved into three capsid proteins, VP4A, B and C. VP4 is also the most conserved gene from Nora virus and related viruses. Nora virus is a non-pathogenic virus found in gut of Drosophila melanogaster. It causes persistent, non-pathological infection, it replicates in the fly gut and is transmitted via the faecal-oral route. Nora virus has a 12333 nucleotides long single-stranded RNA genome of positive polarity.

The V5 tag is derived from a small epitope (Pk) found on the P and V proteins of the paramyxovirus (of the simian virus 5 (SV5) family) and is extensively used as a general epitope tag in expression vectors.

Aspartyl aminopeptidase A (APA) and glutamyl APA, produce angiotensin III (Ang-III) by removing an aspartic acid from the N-terminal of angiotensin-II (Ang-II). Ang-III has many similar biological properties to Ang-II including aldosterone secretion and vasoconstriction, however some of its functions oppose those of Ang-II, such as sodium excretion and secretion of atrial natriuretic peptide (ANP). Due to its ability to promote ANP secretion Ang-III has some cardio protective effects.Ang-III likely binds to both G-protein-coupled Ang-II type 1 (AT1) and Ang-II type 2 (AT2) receptors with a similar affinity to that of Ang-II. Ang-III appears to be cleared from the plasma at a faster rate than Ang-II, therefore the physiological effects of Ang-III are likely to limited to the site at which it is produced.

Histone H3 (1 - 20) K4Me3 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. 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. Like 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 many lysine and arginine residues, they have a positive net charge which interacts electrostatically 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 alter the positioning of the nucleosome, allowing the DNA to be either available or inaccessible to the transcription machinery.Histone tails can undergo multiple modifications, including acetylation, methylation, ubiquitylation and sumoylation.  The modification pattern is believed to alter chromatin function/structure.  Lysine 4 of histone H3 (1 - 20) K4Me3 has been tri-methylated. This is a common cis-tail histone methylation pattern, read by histone effectors such as Spindlin1. H3 (1 - 20) K4Me3 has been used to understand interactions with histone effectors in co-crystallisation.   H3 (1 - 20) K4Me3 is labelled with the Aurora Fluor 647 fluorescent tag.

Codesane (COD), is a cationic α-helical amphipathic-anti-microbial-peptide isolated from the venom of the wild bee Colletes daviesanus (Hymenoptera Colletidae). COD exhibits-anti-microbial-activity against Gram-positive and Gram-negative bacteria and Candida albicans but also noticeable haemolytic activity.COD peptide works by permeating both the outer and inner cytoplasmic membranes of Escherichia coli.

Angiotensin I-converting enzyme (ACE) plays a critical role in blood pressure regulation. There is a rise in conditions linked to hypertension such as heart attacks, strokes, and dementia. This has led to search for novel inhibitors of ACE to regulate blood pressure. Food-derived bioactive peptides have been identified and utilised for their health-promoting abilities. The tripeptide FSY (Phe-Ser-Tyr) was identified from shrimp (Pandalus borealis) protein hydrolysate as a highly potent inhibitor of ACE activity. FSY is capable of being absorbed in the digestive tract to be transported in the blood to the receptors which is a useful feature for clinical application. Further study can provide deeper understanding of FSY potency on ACE function and may lead to drug development.

Pepstatin A was originally purified from Actinomycetes species. The peptide is unusual in containing the amino acid statine (4-amino-hydroxy-6-methylheptanoic acid also known as AMHA). Pepstatin A competitively binds with acid proteases in a highly selective reversible manner to inhibit protease activity. Pepstatin A is ineffective on thiol, neutral and serine proteases. The functions of proteases have been investigated by the application of pepstatin A such as renin, pepsin, bovine chymosin and retroviral proteases from HIV. Characterisation of HIV protease using pepstatin A has been vital in development of HIV treatment to block viral replication. Pepstatin A is also a reagent to disrupt autophagy- this helps characterise the function of proteosome degradation in research such as during influenza A replication and improving drug delivery of therapeutic cancer treatments. Biotin is C-terminally linked to this peptide for convenient detection and purification. The polyethylene glycol (PEG) linker improves the water solubility of biotin labelled proteins.

(Arg)9 is a cationic cell-penetrating peptide (CPP)consisting of 9 arginines. Arginine rich CPPs enter cells in a passive manner through membrane multilamellarity and fusion. Evidently as a CPP, (Arg)9 can function to deliver specific molecules to target cells and can be used for drug delivery purposes.

α-Gliadin (58-73) is derived from Gliadin peptides, the component of wheat involved in the gastrointestinal symptoms of wheat allergy and Celiac Disease (CD). During wheat allergies histamines and leukotrienes are secreted due to gliadin peptide sequences cross-linking two IgE molecules on mast cells and basophils.The glutamine and proline rich peptides of which Gliadin is composed of are resistant to proteolysis during digestion, leaving them active in the gastrointestinal tract. Subsequently these are deamidated by tissue transglutaminase and can bind to HLA-DQ2 or DQ8. As a result in patients with the autoimmune disease CD, there is a Th1-mediated inflammatory immune response against these gliadin peptides.Gliadin can exert additional effects on the intestinal microbiota and ileal barrier function. It has been found that gut microbiota members such as Bifidobacterium and lactobacillus have the ability to digest and inactivate gliadin peptides hence reducing their inflammatory effects in the gastrointestinal system.

Pro B-type natriuretic peptide (Pro-BNP) is secreted from cardiac myocytes and cleaved into BNP and the remaining part of the prohormone N-terminal proBNP (NT-proBNP). When the heart fibres become stretched more BNP and NT-proBNP are released to try and compensate for the increased pressure. During heart failure the walls of the atria become over stretched and thus increase the levels of NT-proBNP detectable. NT-proBNP has a longer half-life than BNP and therefore is detectable at higher levels in blood plasma than BNP. NT-pro-BNP is believed to be cleared by renal excretion, but this is not confirmed. As a diagnostic tool, NT-proBNP (47-76) has become very useful in helping diagnose heart failure and provide a prognosis. The measurement of NT-proBNP (47-76) has been incorporated into management and guidelines of clinical settings. As a research tool it still provides valuable data such as symptoms onset in relation to NT-proBNP levels and how inflammation effects the level of BNP as well as the BNP/ NT-proBNP ratio.