N-Acetyl lysyltyrosylcysteine amide
目录号 : GC60263
N-Acetyllysyltyrosylcysteineamide是一种有效的，可逆的，特异性且无毒的髓过氧化物酶(MPO)三肽抑制剂。N-Acetyllysyltyrosylcysteineamide在体内可有效抑制MPO产生有毒氧化剂。N-Acetyllysyltyrosylcysteineamide减轻中风后大脑的神经元损伤，并保留脑组织和神经功能。N-Acetyllysyltyrosylcysteineamide抑制MPO依赖性次氯酸(HOCl)的生成，蛋白质硝化和LDL氧化。
Cas No.:1287585-40-3
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
N-Acetyl lysyltyrosylcysteine amide is a potent, reversible, specific, and non-toxic tripeptide inhibitor of myeloperoxidase (MPO). N-Acetyl lysyltyrosylcysteine amide effectively inhibits MPO generation of toxic oxidants in vivo. N-Acetyl lysyltyrosylcysteine amide reduces neuronal damage and preserves brain tissue and neurological function in the stroked brain. N-Acetyl lysyltyrosylcysteine amide inhibits MPO-dependent hypochlorous acid (HOCl) generation, protein nitration, and LDL oxidation[1][2].
N-Acetyl lysyltyrosylcysteine amide (KYC) significantly decreases infarct size, blood-brain barrier leakage, infiltration of myeloid cells, loss of neurons, and apoptosis in the brains of middle cerebral artery occlusion (MCAO) mice[1].N-Acetyl lysyltyrosylcysteine amide (10 mg/kg; i.p.; daily for 3-7 days) significantly reduces neurological severity scores and infarct size in MCAO mice[1].N-Acetyl lysyltyrosylcysteine amide (10 mg/kg; i.p.; daily 7 days) significantly protects BBB function and decreased neutrophil infiltration. N-Acetyl lysyltyrosylcysteine amide (10 mg/kg; i.p.; daily 7 days) significantly reduces microglia/macrophage activation and neuron loss in MCAO mice. N-Acetyl lysyltyrosylcysteine amide (10 mg/kg; i.p.; daily for 3-7 days) decreases apoptosis and cell injury in the brains of MCAO mice. N-Acetyl lysyltyrosylcysteine amide reduced MPO in the brains of MCAO mice. N-Acetyl lysyltyrosylcysteine amide reduces NO2Tyr and 4-HNE in MCAO mice[1]. Animal Model: 8-10 weeks old C57BL/6J mice (middle cerebral artery occlusion (MCAO) mode)[1]
[1]. Yu G, et al. Inhibition of myeloperoxidase oxidant production by N-acetyl lysyltyrosylcysteine amide reduces brain damage in a murine model of stroke [published correction appears in J Neuroinflammation. 2016;13(1):166]. J Neuroinflammation. 2016;13(1):119. Published 2016 May 24. [2]. Zhang H, et al. N-acetyl lysyltyrosylcysteine amide inhibits myeloperoxidase, a novel tripeptide inhibitor. J Lipid Res. 2013;54(11):3016-3029.
| Cas No. | 1287585-40-3 | SDF | |
| Canonical SMILES | SC[C@@H](C(N)=O)NC([C@H](CC1=CC=C(O)C=C1)NC([C@H](CCCCN)NC(C)=O)=O)=O | ||
| 分子式 | C20H31N5O5S | 分子量 | 453.56 |
| 溶解度 | H2O : 125 mg/mL (275.60 mM; Need ultrasonic) | 储存条件 | -20°C, protect from light |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.2048 mL | 11.0239 mL | 22.0478 mL |
| 5 mM | 0.441 mL | 2.2048 mL | 4.4096 mL |
| 10 mM | 0.2205 mL | 1.1024 mL | 2.2048 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
N-Acetyl lysyltyrosylcysteine amide inhibits myeloperoxidase, a novel tripeptide inhibitor
J Lipid Res 2013 Nov;54(11):3016-29.PMID:23883583DOI:10.1194/jlr.M038273.
Myeloperoxidase (MPO) plays important roles in disease by increasing oxidative and nitrosative stress and oxidizing lipoproteins. Here we report N-Acetyl lysyltyrosylcysteine amide (KYC) is an effective inhibitor of MPO activity. We show KYC inhibits MPO-mediated hypochlorous acid (HOCl) formation and nitration/oxidation of LDL. Disulfide is the major product of MPO-mediated KYC oxidation. KYC (≤4,000 μM) does not induce cytotoxicity in bovine aortic endothelial cells (BAECs). KYC inhibits HOCl generation by phorbol myristate acetate (PMA)-stimulated neutrophils and human promyelocytic leukemia (HL-60) cells but not superoxide generation by PMA-stimulated HL-60 cells. KYC inhibits MPO-mediated HOCl formation in BAEC culture and protects BAECs from MPO-induced injury. KYC inhibits MPO-mediated lipid peroxidation of LDL whereas tyrosine (Tyr) and tryptophan (Trp) enhance oxidation. KYC is unique as its isomers do not inhibit MPO activity, or are much less effective. Ultraviolet-visible spectral studies indicate KYC binds to the active site of MPO and reacts with compounds I and II. Docking studies show the Tyr of KYC rests just above the heme of MPO. Interestingly, KYC increases MPO-dependent H₂O₂ consumption. These data indicate KYC is a novel and specific inhibitor of MPO activity that is nontoxic to endothelial cell cultures. Accordingly, KYC may be useful for treating MPO-mediated vascular disease.
Inhibition of myeloperoxidase by N-Acetyl lysyltyrosylcysteine amide reduces experimental autoimmune encephalomyelitis-induced injury and promotes oligodendrocyte regeneration and neurogenesis in a murine model of progressive multiple sclerosis
Neuroreport 2018 Feb 7;29(3):208-213.PMID:29266034DOI:10.1097/WNR.0000000000000948.
It is known that oxidative stress produced by proinflammatory myeloid cells plays an important role in demyelination and neuronal injury in progressive multiple sclerosis (MS). Myeloperoxidase (MPO) is a pro-oxidative enzyme released from myeloid cells during inflammation. It has been shown that MPO-dependent oxidative stress plays important roles in inducing tissue injury in many inflammatory diseases. In this report, we treated NOD experimental autoimmune encephalomyelitis (EAE) mice, a murine model of progressive MS, with N-Acetyl lysyltyrosylcysteine amide (KYC), a novel specific MPO inhibitor. Our data showed that KYC treatment not only attenuated MPO-mediated oxidative stress but also reduced demyelination and axonal injury in NOD EAE mice. More importantly, we found that KYC treatment increased oligodendrocyte regeneration and neurogenesis in NOD EAE mice. Taken together, our data suggests that targeting MPO should be a good therapeutic approach for reducing oxidative injury and preserving neuronal function in progressive MS patients.
Inhibition of Myeloperoxidase by N-Acetyl lysyltyrosylcysteine amide Reduces Oxidative Stress-Mediated Inflammation, Neuronal Damage, and Neural Stem Cell Injury in a Murine Model of Stroke
J Pharmacol Exp Ther 2018 Feb;364(2):311-322.PMID:29255000DOI:10.1124/jpet.117.245688.
Recent studies suggest that myeloperoxidase (MPO)-dependent oxidative stress plays a significant role in brain injury in stroke patients. We previously showed that N-Acetyl lysyltyrosylcysteine amide (KYC), a novel MPO inhibitor, significantly decreased infarct size, blood-brain barrier leakage, infiltration of myeloid cells, loss of neurons, and apoptosis in the brains of middle cerebral artery occlusion (MCAO) mice. Inhibition of MPO also noticeably reduced neurologic severity scores of MCAO mice. Thus, our data support the idea that MPO-dependent oxidative stress plays a detrimental role in tissue injury in ischemic stroke. However, the mechanisms of MPO-induced injury in stroke are still largely unknown. Here, we present new evidence showing that KYC treatment greatly reduced inflammation by decreasing the number of proinflammatory M1 microglial cells and N1 neutrophils in the brains of MCAO mice. KYC also markedly reduced the expression of high-mobility group box 1, receptor for advanced glycation end products, and nuclear factor-κB in the brains of MCAO mice. Both neurons and neural stem cells (NSCs) were oxidatively injured by MPO-dependent oxidative stress in MCAO mice. Inhibiting MPO-dependent oxidative stress with KYC significantly reduced oxidative injury and apoptosis in neurons and NSCs. KYC treatment also protected transplanted exogenous NSCs in the brains of MCAO mice. Thus, our studies suggest that MPO-dependent oxidative stress directly injures brain tissues by oxidizing neurons and NSCs and increasing inflammation during stroke. Inhibition of MPO activity with KYC preserves neuronal function and helps the brain recover from injury after stroke.
Inhibition of myeloperoxidase oxidant production by N-Acetyl lysyltyrosylcysteine amide reduces brain damage in a murine model of stroke
J Neuroinflammation 2016 May 24;13(1):119.PMID:27220420DOI:10.1186/s12974-016-0583-x.
Background: Oxidative stress plays an important and causal role in the mechanisms by which ischemia/reperfusion (I/R) injury increases brain damage after stroke. Accordingly, reducing oxidative stress has been proposed as a therapeutic strategy for limiting damage in the brain after stroke. Myeloperoxidase (MPO) is a highly potent oxidative enzyme that is capable of inducing both oxidative and nitrosative stress in vivo. Methods: To determine if and the extent to which MPO-generated oxidants contribute to brain I/R injury, we treated mice subjected to middle cerebral artery occlusion (MCAO) with N-Acetyl lysyltyrosylcysteine amide (KYC), a novel, specific and non-toxic inhibitor of MPO. Behavioral testing, ischemic damage, blood-brain-barrier disruption, apoptosis, neutrophils infiltration, microglia/macrophage activation, and MPO oxidation were analyzed within a 7-day period after MCAO. Results: Our studies show that KYC treatment significantly reduces neurological severity scores, infarct size, IgG extravasation, neutrophil infiltration, loss of neurons, apoptosis, and microglia/macrophage activation in the brains of MCAO mice. Immunofluorescence studies show that KYC treatment reduces the formation of chlorotyrosine (ClTyr), a fingerprint biomarker of MPO oxidation, nitrotyrosine (NO2Tyr), and 4-hydroxynonenal (4HNE) in MCAO mice. All oxidative products colocalized with MPO in the infarcted brains, suggesting that MPO-generated oxidants are involved in forming the oxidative products. Conclusions: MPO-generated oxidants play detrimental roles in causing brain damage after stroke which is effectively reduced by KYC.
Myeloperoxidase instigates proinflammatory responses in a cecal ligation and puncture rat model of sepsis
Am J Physiol Heart Circ Physiol 2020 Sep 1;319(3):H705-H721.PMID:32762560DOI:10.1152/ajpheart.00440.2020.
Myeloperoxidase (MPO)-derived hypochlorous (HOCl) reacts with membrane plasmalogens to yield α-chlorofatty aldehydes such as 2-chlorofatty aldehyde (2-ClFALD) and its metabolite 2-chlorofatty acid (2-ClFA). Recent studies showed that 2-ClFALD and 2-ClFA serve as mediators of the inflammatory responses to sepsis by as yet unknown mechanisms. Since no scavenger for chlorinated lipids is available and on the basis of the well-established role of the MPO/HOCl/chlorinated lipid axis in inflammatory responses, we hypothesized that treatment with MPO inhibitors (N-Acetyl lysyltyrosylcysteine amide or 4-aminobenzoic acid hydrazide) would inhibit inflammation and proinflammatory mediator expression induced by cecal ligation and puncture (CLP). We used intravital microscopy to quantify in vivo inflammatory responses in Sham and CLP rats with or without MPO inhibition. Small intestines, mesenteries, and lungs were collected to assess changes in MPO-positive staining and lung injury, respectively, as well as free 2-ClFA and proinflammatory mediators levels. CLP caused neutrophil infiltration, 2-ClFA generation, acute lung injury, leukocyte-/platelet-endothelium interactions, mast cell activation (MCA), plasminogen activator inhibitor-1 (PAI-1) production, and the expression of several cytokines, chemokines, and vascular endothelial growth factor, changes that were reduced by MPO inhibition. Pretreatment with a PAI-1 inhibitor or MC stabilizer prevented CLP-induced leukocyte-endothelium interactions and MCA, and abrogated exogenous 2-ClFALD-induced inflammatory responses. Thus, we provide evidence that MPO instigates these inflammatory changes in CLP and that chlorinated lipids may serve as a mechanistic link between the enzymatic activity of MPO and PAI-1- and mast cell-dependent adhesive interactions, providing a rationale for new therapeutic interventions in sepsis.NEW & NOTEWORTHY Using two distinct myeloperoxidase (MPO) inhibitors, we show for the first time that MPO plays an important role in producing increases in free 2-chlorofatty aldehyde (2-ClFALD)-a powerful proinflammatory chlorinated lipid in plasma and intestine-a number of cytokines and other inflammatory mediators, leukocyte and platelet rolling and adhesion in postcapillary venules, and lung injury in a cecal ligation and puncture model of sepsis. In addition, the use of a plasminogen activator inhibitor-1 (PAI-1) inhibitor or a mast cell stabilizer prevented inflammatory responses in CLP-induced sepsis. PAI-1 inhibition also prevented the proinflammatory responses to exogenous 2-ClFALD superfusion. Thus, our study provides some of the first evidence that MPO-derived free 2-ClFA plays an important role in CLP-induced sepsis by a PAI-1- and mast cell-dependent mechanism.