Enzyme Modulators

<p>The sequence of this peptide has been derived from a highly conserved region of the T-cell phosphatase TC.PTP45 and is an excellent general substrate for protein tyrosine phosphatases.The protein tyrosine phosphatase (PTP) superfamily has 103 enzymes that catalyse substrate dephosphorylation at tyrosine residues through a covalent enzyme intermediate involving a thiophosphate linkage from the active site cysteine residue. All PTPs share a common signature motif (I/V)HCXAGXGR(S/T), named the P-loop, responsible for the enzyme activity. The PTP superfamily can be divided into four classes based on their cellular localization/catalytic domains: the receptor-like PTPs (rPTPs), the non-receptor PTPs (nrPTPs), the low molecular weight PTP (LMWPTP), and the VH-1 and CDC-25 groups.PTPs are involved in regulating a plethora of cellular activities, including proliferation and differentiation, survival, migration, metabolism, and the immune response. Abnormal protein tyrosine phosphorylation has been associated with the etiology of various human diseases, including cancer, diabetes, and autoimmune dysfunctions, therefore making PTPs novel therapeutic targets.</p>

<p>Cyclin-dependent kinases (CDKs) are a family of kinases that regulate the cell cycle and gene transcription. Cyclin-dependent kinase 7 (CDK7) forms a trimeric complex with cyclin H and MAT1, which functions as a Cdk-activating kinase (CAK) and promotes cell cycle progression. CDK7 is an essential component of the transcription factor TFIIH, involved in DNA repair. CDK7 is also implicated in mRNA processing, transcription activation, pause induction, and pause release.CDK8 associates with the mediator complex and regulates transcription via several mechanisms, including influencing binding of RNA polymerase II to the mediator complex. CDK8 phosphorylates the Notch intracellular domain, SREBP, and STAT1. Its regulatory subunit is cyclin C. CDK9 is a component of the TAK/P-TEFb complex, which phosphorylates the part of RNA polymerase II. Its regulatory subunit is cyclin T or cyclin K. CDK9 interacts with HIV-1 Tat protein and TRAF2, and is involved in the differentiation of skeletal muscle.CDKs are often over expressed in cancers and may correlate with poor prognosis. This peptide is based on the C-terminal of RNA polymerase II and is used in kinase assays.</p>

<p>Ile-Pro-Pro (IPP) has the ability to inhibit angiotensin-converting enzyme and stimulate the production of nitric oxide. It could be used to improve hypertension thus reducing the risk of cardiovascular diseases.</p>

<p>Proprotein convertase subtilisin/kexin type 9 (PCSK9) is negative regulator of hepatic low-density lipoprotein (LDL) receptors by promoting their degradation. This leads to an increase in plasma levels of cholesterol-LDL (LDL-c). PCSK9 binds to the LDL receptor at the epidermal growth factor precursor homology domain A (EGF-A) which leads the receptor to be targeted for degradation. Natural loss of function mutations in PCSK9 have been linked to improved coronary health and lower cholesterol levels with reduced risk of coronary heart disease. This has led to further study to find inhibitors of PCSK9 with the hope that they may be clinically relevant in the future.As discussed, PCSK9 binds to EGF-A on the LDL receptor. A peptide named pep 2-8 is a mimic of EGF-A and binds PCSK9 in the same manner observed with the LDL receptor. Pep 2-8 is a potent selective competitive inhibitor of PCSK9. Pep 2-8 restores LDL receptor function and LDL uptake of PCSK9-treated HepG2 cells. This is still an active area of research to optimise inhibition of PCSK9 for cholesterol regulation.Pep 2-8 has also been utilised as an anchor peptide in phage-display experiments to bind an extension peptide library to the groove site.Peptide Ac-TVFTSWEEYLDWV-NH2 is a Research Peptide with significant interest within the field academic and medical research. This peptide is available for purchase at Cymit Quimica in multiple sizes and with a specification of your choice.</p>

<p>Abltide represents the optimal substrate peptide of Abl (or c-Abl), a non-receptor tyrosine kinase (NRTK) and the oncogenic Bcr-Abl tyrosine kinase (TK) (formed via a fusion between the Abelson (Abl) TK gene and the break point cluster region protein Brc). Abl was discovered as the gene from which the Abelson leukaemia virus derived its Gag-v-Abl oncogene.TKs are critical enzymes involved in multiple signalling pathways. However, Tks can promote cancer progression when deregulated, for example deregulated TK, Bcr-Abl gives rise to chronic myeloid leukaemia (CML) and Philadelphia chromosome-positive acute lymphocytic leukaemia (Ph+ ALL).Abl is activated by various signals including: growth factors, cytokines, cell adhesion, DNA damage and oxidative stress and results in the stimulation of both pro- and anti-apoptotic roles, cell proliferation or differentiation, retraction, or migration. Abl phosphorylates a large number of functionally diverse substrates, in part due to its ability to shuttle between the cytosol and the nucleus and bind both DNA and actin&amp;mdash-two biopolymers with fundamental roles in almost all biological processes.</p>

<p>H-FERQHM-OH peptide, corresponding to RNase A 8-13 (Chain A of bovine pancreatic ribonuclease) is a non-amyloidogenic peptide, that can be used as a negative control in amyloid formation experiments together with CRB1001320.</p>

<p>eV1-2 is a selective εPKC inhibitor peptide which interferes with protein-protein interactions between the ϵPKC isozyme and its anchoring protein (ϵRACK). ϵPKC and ϵRACK regulate the contraction rate of heart muscle cells and provide protection from ischemia induced cell death. ϵV1-2 is derived from the C2 domain of ϵPKC, a region important for protein-protein interactions and thus acts as a competitive inhibitor of these interactions. The C2 region is well conserved between species, but different enough from other PKC isozymes to allow for targeted inhibition (ϵV1-2 is 88% identical between sea slugs and rat ϵPKC, yet only 36% identical between rat ϵPKC and rat θ´PKC). This peptide contains a C-terminal cysteine residue for conjugation to a carrier protein.</p>

<p>Acid α-glucosidase (83-99) (human) is derived from the exogenous enzyme which degrades glycogen, maltose and isomaltose through targeting alpha -1,4 and alpha -1,6 linkages. Once synthesised in its precursor form, within the Golgi it is glycosylated and acquires mannose 6-phosphate residues. This allows it to be transported to the Lysosome in a multistep process.Pompe disease, also known as glycogen storage disease type II, can be diagnosed through the absence of acid α-glucosidase activity within patients. Therefore glycogen degradation in the lysosome is inhibited by this autosomal recessive disorder. This results in the accumulation of glycogen and tissue destruction, hence contributing to the pathologies of muscle weakness and respiratory failure, associated with infantile onset and adult onset Pompe disease.</p>

<p>ERKtide Substrate Peptide.</p>

<p>This peptide is phosphorylated by Janus kinase 2 (JAK2) and is an ideal substrate for use in kinase assays. The JAK family of kinases is essential for the signalling of a host of immune modulators in tumour, stromal, and immune cells where they are highly expressed. JAK family proteins mediate the signalling of the interferon (IFN), IL-6, and IL-2 families of cytokines.JAK kinases are associated with cytokine receptors. Cytokine binding to these receptors results in activation of JAK kinases and receptor phosphorylation. Phosphorylated cytokine receptors recruit STAT proteins, which are then phosphorylated by the activated JAK kinases. Phosphorylated STAT proteins form homo- and hetero-dimers that translocate into the nucleus and function as transcription factors.</p>

<p>During extraction of lecithin from egg yolk, peptide by-products can be isolated and purified by gel filtration. Within the by-products this has led to the discovery of biologically active value-added products. The egg yolk gel filtration (EFGF) fractions were analysed for their antioxidant and angiotensin converting enzyme (ACE) inhibitory activities. EYGF-33 predominantly contained 3 peptides - KLSDW, YPSPV, and MPVHTDAD). YPSPV in EYGF-33 was found to have minimal antioxidant activity. However, YPSPV showed notably high angiotensin converting enzyme (ACE) inhibitory activity, it exceeded the positive control captopril.</p>

<p>A15 also known as alpha2-Antiplasmin is a serine/protease inhibitor which inactivates plasmin in the blood. To inhibit plasmin in the blood alpha2-Antiplasmin forms a protease serpin complex with plasmin due to interactions of kringle 1 or 3 of plasmin and the lysine residues of alpha2-Antiplasmin's C-terminus. Although synthesised in the Liver A15 is also present within the neurons of the human brain and its expression has been found to be enhanced in Aβ plaques of Alzheimer's disease and during myocardial infarction. A high concentration of alpha2-Antiplasmin in the blood may also contribute to an increased risk of Ischemic strokes. Alternatively its expression appears to be diminished in patients with cirrhosis and acute liver failure. A further function of A15 is its ability to regulate fibrinolysis through crosslinking to fibrin.</p>

<p>DARKtide is a substrate peptide for death-associated protein kinase (DAPK) for use in kinases assays. DAPK is involved in several cellular pathways including: apoptosis, tumour suppression, stress response, anti-viral immunity and IL-1-associated inflammatory diseases. In C. elegans DAPK-1 regulates epidermal morphogenesis, innate immunity and wound repair.</p>

<p>Amino acids 651-660 of Poly(ADP-ribose) polymerase 1 (PARP1). PARP1 is a nuclear DNA repair enzyme that binds to DNA when damage is detected. PARP1 coordinates double and single strand break repair by first cleaving NAD+ into nicotinamide and ADP-ribose, and then synthesising poly-(ADP-ribose) (PAR) chains from ADP-ribose on target proteins (PARylation). PARylation of histone proteins mediates the relaxation of the chromatin and recruitment of DNA-break repair enzymes.PARP1 can also act as a transcriptional co-activator, modulating the expression of itself and many other genes by direct binding to or PARylation of enhancers and promoters. PARP1 is also involved in maintaining mtDNA.PARP1 belongs to the PARP family which has 7 known and 10 putative members. PARP1 accounts for &gt;85% of the PARP activity in cellular systems.</p>

<p>Axltide-is a substrate peptide for use in kinase assays and is based on the mouse insulin receptor substrate 1 (IRS1) (amino acid 979-989).IRS1 is a membrane-proximal adaptor protein, which binds to, and is phosphorylated by, the insulin receptor (IR) at its tyrosine residue. IRS1 transmits the extracellular signal for insulin to serine/threonine kinases, such as Akt which then deliver the signal into the cell to mediate the various actions of insulin.</p>

<p>Substrate for proline-rich tyrosine kinase 2 (Pyk2)- can be used for substrate phosphorylation assays. Pyk2 is a member of the focal adhesion kinase (FAK) subfamily of cytoplasmic tyrosine kinases. Pyk2 is also known as: calcium-dependent tyrosine kinase (CADTK)- cellular adhesion kinase β- related adhesion focal tyrosine kinase (RAFTK)- or FAK2.Pyk2 functions as a scaffold protein, and it interacts with cytoplasmic proteins at focal adhesion sites to integrate different environmental signals. Pyk2 is activated by several stimuli, including elevated intracellular calcium levels, protein kinase C activation, and exposure to stress factors. Recently, Pyk2 has become a potentially important new therapeutic target or prognostic marker because overexpression of Pyk2 has been found in many human tumours.</p>

<p>ERKtide Substrate Peptide.</p>

<p>During extraction of lecithin from egg yolk, peptide by-products can be isolated and purified by gel filtration. Within the by-products this has led to the discovery of biologically active value-added products. The egg yolk gel filtration (EFGF) fractions were analysed for their antioxidant and angiotensin converting enzyme (ACE) inhibitory activities. EYGF-56 predominantly contained 3 peptides - SDNRNQGY, KGLWE, and IQVPL. KGLWE in EYGF-56 was found to have very strong antioxidant activity. KGLWE showed minimal angiotensin converting enzyme (ACE) inhibitory activity.</p>

<p>During extraction of lecithin from egg yolk, peptide by-products can be isolated and purified by gel filtration. Within the by-products this has led to the discovery of biologically active value-added products. The egg yolk gel filtration (EFGF) fractions were analysed for their antioxidant and angiotensin converting enzyme (ACE) inhibitory activities. EYGF-56 predominantly contained 3 peptides - SDNRNQGY, IQVPL, and KGLWE. IQVPL in EYGF-56 was found to have minimal antioxidant activity. YPSPV showed some angiotensin converting enzyme (ACE) inhibitory activity.</p>

<p>The peptide IRW, characterised from egg protein, exhibits inhibitory properties against the angiotensin converting enzyme (ACE2) and could be used to prevent cardiovascular disease with further research. Treatment of hypertensive mice with IRW induced endothelium-dependent vasorelaxation and reduced vascular inflammation. The IRW tripeptide acts as anti-hypertensive by upregulating ACE2 activity via the Mas receptor (MasR) and upregulating Akt/eNOS signalling in the aorta. IRW also induces superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activity. These may play a factor in IRW's role as an anti-inflammatory. IRW shows promise as a nutraceutical for inflammatory conditions and a tool for drug development in cardiovascular disease.</p>