N-Acetyl-Ser-Asp-Lys-Pro
(Synonyms: 戈雷拉肽,Ac-SDKP) 目录号 : GC33889
N-Acetyl-Ser-Asp-Lys-Pro是ACE的N-末端位点的天然和特异性底物。
Cas No.:127103-11-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
N-Acetyl-Ser-Asp-Lys-Pro is a natural and specific substrate for the N-terminal site of ACE.
N-Acetyl-Ser-Asp-Lys-Pro is an endogenous tetrapeptide secreted by bone marrow and is ubiquitously found in plasma and various tissues. N-Acetyl-Ser-Asp-Lys-Pro is degraded specifically by ACE, and its plasma level rises substantially during ACE inhibitor therapy. N-Acetyl-Ser-Asp-Lys-Pro inhibits the proliferation of isolated cardiac fibroblasts but significantly stimulates the proliferation of vascular smooth muscle cells. Flow cytometry of rat cardiac fibroblasts treated with N-Acetyl-Ser-Asp-Lys-Pro shows significant inhibition of the progression of cells from G0/G1 phase to S phase of the cell cycle. In cardiac fibroblasts transfected with a Smad-sensitive luciferase reporter construct, N-Acetyl-Ser-Asp-Lys-Pro decreases luciferase activity by 55%. Moreover, phosphorylation and nuclear translocation of Smad2 is decreased in cardiac fibroblasts treated with N-Acetyl-Ser-Asp-Lys-Pro[1]. N-acetyl-seryl-aspartyl-lysyl-proline is a negative regulator of hematopoietic stem cell proliferation. N-acetyl-seryl-aspartyl-lysyl-proline is involved in the control of hematopoietic stem cell proliferation by preventing their recruitment into S-phase. N-acetyl-seryl-aspartyl-lysyl-proline appears to exert this function by blocking the action of a stem cell-specific proliferation stimulator and acts selectively on quiescent progenitors[2]. N-Acetyl-Ser-Asp-Lys-Pro inhibits collagenase expression and activation is associated with increased expression of TIMP-1 and TIMP-2. N-Acetyl-Ser-Asp-Lys-Pro does not alter collagenase or gelatinase activity in cardiac fibroblasts under basal conditions, but blunts the IL-1β-induced increase in total collagenase activity. Similarly, N-Acetyl-Ser-Asp-Lys-Pro normalizes the IL-1β-mediated increase in MMP-2 and MMP-9 activities and MMP-13 expression[3].
N-Acetyl-Ser-Asp-Lys-Pro prevents hypertension-induced inflammatory cell infiltration, collagen deposition, nephrin downregulation and albuminuria, which could lead to renoprotection in hypertensive mice[4].
[1]. Rousseau A, et al. The hemoregulatory peptide N-acetyl-Ser-Asp-Lys-Pro is a natural and specificsubstrate of the N-terminal active site of human angiotensin-converting enzyme. J Biol Chem. 1995 Feb 24;270(8):3656-61. [2]. Pokharel S, et al. N-acetyl-Ser-Asp-Lys-Pro inhibits phosphorylation of Smad2 in cardiac fibroblasts. Hypertension. 2002 Aug;40(2):155-61. [3]. Rhaleb NE, et al. N-acetyl-Ser-Asp-Lys-Pro inhibits interleukin-1β-mediated matrix metalloproteinase activation in cardiac fibroblasts. Pflugers Arch. 2013 Oct;465(10):1487-95. [4]. Rhaleb NE, et al. Renal protective effects of N-acetyl-Ser-Asp-Lys-Pro in deoxycorticosterone acetate-salt hypertensive mice. J Hypertens. 2011 Feb;29(2):330-8.
| Cas No. | 127103-11-1 | SDF | |
| 别名 | 戈雷拉肽,Ac-SDKP | ||
| Canonical SMILES | Ac-Ser-Asp-Lys-Pro | ||
| 分子式 | C20H33N5O9 | 分子量 | 487.5 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
| 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。 |
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| 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.0513 mL | 10.2564 mL | 20.5128 mL |
| 5 mM | 0.4103 mL | 2.0513 mL | 4.1026 mL |
| 10 mM | 0.2051 mL | 1.0256 mL | 2.0513 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 |
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| % 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。
Antifibrotic peptide N-Acetyl-Ser-Asp-Lys-Pro (Ac-SDKP): opportunities for angiotensin-converting enzyme inhibitor design
Clin Exp Pharmacol Physiol 2013 Aug;40(8):535-41.PMID:23351021DOI:10.1111/1440-1681.12062.
The renin-angiotensin system (RAS) is central to regulation of blood pressure and electrolyte homeostasis. Angiotensin-converting enzyme (ACE), a key protease in the RAS, has a range of substrates, including N-Acetyl-Ser-Asp-Lys-Pro (Ac-SDKP). The peptide Ac-SDKP is cleared almost exclusively by ACE, and specifically by the N-domain active site of this enzyme. N-Acetyl-Ser-Asp-Lys-Pro is a negative regulator of haematopoietic stem cell differentiation and is a potent antifibrotic agent. In this review, the physiological actions of Ac-SDKP are presented, together with the potential clinical usefulness of raising Ac-SDKP levels. This emphasizes the possible opportunity of N-domain-selective ACE inhibitors or ACE-resistant Ac-SDKP analogues for the treatment of fibrosis.
Urine N-Acetyl-Ser-Asp-Lys-Pro measurement as a versatile biomarker to assess adherence to angiotensin-converting enzyme inhibitors
J Hypertens 2022 Feb 1;40(2):348-355.PMID:34508023DOI:10.1097/HJH.0000000000003018.
Background: Poor adherence to treatment is a major health issue in hypertension. The large number of drugs to be detected limits the implementation of chemical adherence testing by liquid chromatography/mass spectrometry (LC-MS/MS). AcSDKP, a peptide accumulating in the presence of angiotensin-converting-enzyme inhibitor (ACEI) treatment, has been validated as a proven marker of adherence by enzyme-linked immunosorbent assay. Our aim was to validate urine measurements of AcSDKP compared with active metabolites of various ACEI, measured simultaneously by LC-MS/MS. Method: We first studied the time-dependent relationships between urinary perindoprilat and AcSDKP in a pharmacokinetic/pharmacodynamic study in healthy volunteers. We then compared the sensitivity and specificity of urinary AcSDKP vs. three ACEI active metabolites (enalaprilat, perindoprilat, ramiprilat) taken as reference to detect nonadherence in spot urine samples from a prospective cohort of hypertensive outpatients. Results: The urinary excretion profiles of AcSDKP and perindoprilat were similar, exhibited a significant correlation, and showed excellent agreement in healthy volunteers. In patients, we found a similar agreement between AcSDKP and the three ACEI metabolites urinary concentrations. The sensitivity and specificity for adherence assessment of urine AcSDKP was 92.2 and 100%, respectively. We observed a difference in the evaluation of good adherence between ACEI metabolites (85.7%) and AcSDKP (79.0%) because of discrepancies in samples where AcSDKP reached undetectability quicker than ACEI metabolites. This characteristic of AcSDKP is of particular interest and could better reflect the true adherence status of patients. Conclusion: Overall, spot urine AcSDKP measurement by LC-MS/MS is a reliable marker of the intake of ACEI treatment and could substitute ACEI metabolites detection.
N-Acetyl-Ser-Asp-Lys-Pro inhibits interleukin-1β-mediated matrix metalloproteinase activation in cardiac fibroblasts
Pflugers Arch 2013 Oct;465(10):1487-95.PMID:23652767DOI:10.1007/s00424-013-1262-8.
Myocardial matrix turnover involves a dynamic balance between collagen synthesis and degradation, which is regulated by matrix metalloproteinases (MMPs). N-Acetyl-Ser-Asp-Lys-Pro (Ac-SDKP) is a small peptide that inhibits cardiac inflammation and fibrosis. However, its role in MMP regulation is not known. Thus, we hypothesized that Ac-SDKP promotes MMP activation in cardiac fibroblasts and decreases collagen deposition via this mechanism. To that end, we tested the effects of Ac-SDKP on interleukin-1β (IL-1β; 5 ng/ml)-stimulated adult rat cardiac fibroblasts. We measured total collagenase activity, MMP-2, MMP-9, and MMP-13 expressions, and activity along with their inhibitors, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. In order to examine the effects of Ac-SDKP on the signaling pathway that controls MMP transcription, we also measured nuclear factor-κB (NFκB) and p42/44 mitogen-activated protein kinase (MAPK) activation. Ac-SDKP did not alter collagenase or gelatinase activity in cardiac fibroblasts under basal conditions, but blunted the IL-1β-induced increase in total collagenase activity. Similarly, Ac-SDKP normalized the IL-1β-mediated increase in MMP-2 and MMP-9 activities and MMP-13 expression. Inhibition of MMPs by Ac-SDKP was associated with increased TIMP-1 and TIMP-2 expressions. Collagen production was not affected by Ac-SDKP, IL-1β, or a combination of both agents. Ac-SDKP blocked IL-1β-induced p42/44 phosphorylation and NFκB activation in cardiac fibroblasts. We concluded that the Ac-SDKP-inhibited collagenase expression and activation was associated with increased expression of TIMP-1 and TIMP-2. These pharmacological effects of Ac-SDKP may be linked to the inhibition of MAPK and NFκB pathway.
N-Acetyl-Ser-Asp-Lys-Pro inhibits phosphorylation of Smad2 in cardiac fibroblasts
Hypertension 2002 Aug;40(2):155-61.PMID:12154106DOI:10.1161/01.hyp.0000025880.56816.fa.
N-Acetyl-Ser-Asp-Lys-Pro (AcSDKP) is a specific substrate for the N-terminal site of ACE and increases 5-fold during ACE inhibitor therapy. It is known to inhibit the proliferation of hematopoietic stem cells and has also recently been reported to inhibit the growth of cardiac fibroblasts. We investigated its mode of action in cardiac fibroblasts by assessing its influence on transforming growth factor beta(1) (TGFbeta1)-mediated Smad signaling. AcSDKP inhibited the proliferation of isolated cardiac fibroblasts (P<0.05) but significantly stimulated the proliferation of vascular smooth muscle cells. Flow cytometry of rat cardiac fibroblasts treated with AcSDKP showed significant inhibition of the progression of cells from G0/G1 phase to S phase of the cell cycle. In cardiac fibroblasts transfected with a Smad-sensitive luciferase reporter construct, AcSDKP decreased luciferase activity by 55+/-9.7% (P=0.01). Moreover, phosphorylation and nuclear translocation of Smad2 was decreased in cardiac fibroblasts treated with AcSDKP. To conclude, AcSDKP inhibits the growth of cardiac fibroblasts and also inhibits TGFbeta1-stimulated phosphorylation of Smad2. Because AcSDKP increases substantially during ACE inhibitor therapy, this suggests a novel pathway independent of angiotensin II, by which ACE inhibitors can inhibit cardiac fibrosis.
The hemoregulatory peptide N-Acetyl-Ser-Asp-Lys-Pro is a natural and specific substrate of the N-terminal active site of human angiotensin-converting enzyme
J Biol Chem 1995 Feb 24;270(8):3656-61.PMID:7876104DOI:10.1074/jbc.270.8.3656.
Angiotensin I-converting enzyme (ACE) is a zinc-dipeptidyl carboxypeptidase, which contains two similar domains, each possessing a functional active site. Respective involvement of each active site in the degradation of the circulating peptide N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP), a negative regulator of hematopoietic stem cell proliferation, was studied by using wild-type recombinant ACE and two full-length mutants containing a single functional site. Both the N- and C-active sites of ACE exhibit dipeptidyl activity toward AcSDKP, with Km values of 31 and 39 microM, respectively. However, the N-active site hydrolyzes the peptide 50 times faster compared with the C-active site, with kcat/Km values of 0.5 and 0.01 microM-1.s-1, respectively. The predominant role of the N-active site in AcSDKP hydrolysis was confirmed by the inhibition of hydrolysis using a monoclonal antibody specifically directed against the N-active site. The N-domain specificity for AcSDKP will aid the identification of specific inhibitors for this domain. This is the first report of a highly specific substrate for the N-active site of ACE, with kinetic constants in the range of physiological substrates, suggesting that ACE might be involved via its N-terminal active site in the in vivo regulation of the local concentration of this hemoregulatory peptide.