Peptides

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.

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 (551-565) 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.

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 (226-240) 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.

[Pyr1]-Apelin-13 acts as a ligand for the apelin receptor (APJ) G protein-coupled receptor and is a substrate for angiotensin-converting enzyme 2. Apelin is a member of the adipokine hormone family from adipose tissue. Adipokines are involved in processes such as vascular homeostasis and angiogenesis.Apelin and the apelin receptor are widely distributed throughout the body. Apelin is associated with cardiovascular diseases, obesity, diabetes and cancer. Apelin is expressed in the spinal cord and the human brain. Immunohistochemistry shows that apelin-17 is significantly expressed in the human heart, brain, lungs and endothelial cells. Studies show myocardial infarction apelin mRNA expression is greater during human heart failure than in healthy tissue. Apelin protects against heart failure due to the pyroglutamic form of apelin, [Pyr1]-Apelin-13, which decreases infarct size of myocardial infarctions. Furthermore, rats with hypertension have reduced levels of apelin and APJ. [Pyr1]-Apelin-13 exhibits higher APJ agonist potency than Apelin-13. We also have the alternative available.

Peptide substrate of the epidermal growth factor receptor (EGFR), a member of the receptor tyrosine kinase family known as ErbBs or HER receptors. These receptors are involved in the regulation of cell proliferation, survival, differentiation and migration. When these receptors are dysregulated many diseases, including cancer, can arise.Binding to the ligand binding domain of the EGFR causes receptor dimerization. This is sequentially followed by the tyrosine kinase domain being activated and the tyrosine residues on the C-terminal tail of the receptor becoming phosphorylated, activating downstream signalling pathways.This peptide contains an N-terminal 5-Carboxyfluorescein (5-FAM) moiety, a widely used green fluorescent tag.

Mammalian bombesin-like neuropeptide first isolated from pig spinal cord, which can stimulate rat uterine smooth muscle contraction and gastrin and somatostatin secretion in vitro. Increases blood pressure and pancreatic exocrine secretion in dogs.

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.