Bradykinin 1-5
目录号 : GC32592
Bradykinin(1-5)是Bradykinin的主要稳定代谢物，由血管紧张素转换酶(ACE)经蛋白水解作用形成。
Cas No.:23815-89-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Bradykinin (1-5) is a major stable metabolite of Bradykinin, formed by the proteolytic action of angiotensin-converting enzyme (ACE).
Bradykinin is a short-lived vasoactive peptide, with a reported half-life in vivo of 17 s, that is rapidly metabolized in the circulation to Bradykinin (1-5). Bradykinin (1-5), the product of two sequential cleavages of Bradykinin by ACE at the Pro7-Phe8 and Phe5-Ser6bonds, has been identified as the major stable metabolite of Bradykinin in vivo in human subjects, with a terminal half-life of minutes. Both Bradykinin and Bradykinin (1-5) inhibit α- and γ-thrombin-induced platelet aggregation (P<0.01 versus baseline). Bradykinin (1-5) inhibits γ-thrombin-induced platelet aggregation 50% at a calculated dose of 183±3 pmol/min. Neither Bradykinin nor Bradykinin (1-5) affects thrombin receptor-activating peptide-induced platelet aggregation, consistent with the hypothesis that Bradykinin and Bradykinin 1-5 inhibit thrombin-induced platelet aggregation by preventing cleavage of the thrombin receptor and liberation of thrombin receptor-activating peptide. Bradykinin (1-5) significantly attenuates α-thrombin-induced platelet aggregation but not TRAP 1-6-induced platelet aggregation. Bradykinin (1-5) potently inhibits γ-thrombin (500 nM)-induced platelet aggregation with an ED50 of 183±2 pmol/min[1].
[1]. Murphey LJ, et al. Bradykinin and its metabolite Bradykinin 1-5 inhibit thrombin-induced platelet aggregation in humans. J Pharmacol Exp Ther. 2006 Sep;318(3):1287-92.
| Cas No. | 23815-89-6 | SDF | |
| Canonical SMILES | Arg-Pro-Pro-Gly-Phe | ||
| 分子式 | C27H40N8O6 | 分子量 | 572.66 |
| 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 | 1.7462 mL | 8.7312 mL | 17.4624 mL |
| 5 mM | 0.3492 mL | 1.7462 mL | 3.4925 mL |
| 10 mM | 0.1746 mL | 0.8731 mL | 1.7462 mL |
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| 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 | ||||||||||
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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。
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Bradykinin and its metabolite Bradykinin 1-5 inhibit thrombin-induced platelet aggregation in humans
J Pharmacol Exp Ther 2006 Sep;318(3):1287-92.PMID:16772538DOI:10.1124/jpet.106.104026.
Bradykinin 1-5 is a major stable metabolite of bradykinin, formed by the proteolytic action of angiotensin-converting enzyme. In vitro and animal studies suggest that Bradykinin 1-5 possesses biological activity. This study tests the hypothesis that Bradykinin 1-5 affects vasodilation, fibrinolysis, or platelet aggregation in humans. Graded doses of bradykinin (47-377 pmol/min) and Bradykinin 1-5 (47-18,850 pmol/min) were infused in the brachial artery in random order in 36 healthy subjects. Forearm blood flow (FBF) was measured, and simultaneously obtained venous and arterial plasma samples were analyzed for tissue plasminogen activator (t-PA) antigen. In seven subjects each, alpha- and gamma-thrombin-induced platelet aggregation was measured in platelet-rich plasma obtained from antecubital venous blood at baseline and during peptide infusions. Bradykinin caused dose-dependent increases in FBF and net t-PA release (P < 0.001 for both). Bradykinin 1-5 did not affect FBF (P = 0.13) or net t-PA release (P = 0.46) at concentrations >1500 times physiologic. In contrast, both bradykinin and Bradykinin 1-5 inhibited alpha-and gamma-thrombin-induced platelet aggregation (P < 0.01 versus baseline). Bradykinin 1-5 inhibited gamma-thrombin-induced platelet aggregation 50% at a calculated dose of 183 +/- 3 pmol/min. Neither bradykinin nor Bradykinin 1-5 affected thrombin receptor-activating peptide-induced platelet aggregation, consistent with the hypothesis that bradykinin and Bradykinin 1-5 inhibit thrombin-induced platelet aggregation by preventing cleavage of the thrombin receptor and liberation of thrombin receptor-activating peptide. This study is the first to demonstrate biological activity of Bradykinin 1-5 following in vivo administration to humans. By inhibiting thrombin-induced platelet aggregation without causing vasodilation, Bradykinin 1-5 may provide a model for small molecule substrate-selective thrombin inhibitors.
Conformations of Prolyl-Peptide Bonds in the Bradykinin 1-5 Fragment in Solution and in the Gas Phase
J Am Chem Soc 2016 Jul 27;138(29):9224-33.PMID:27366919DOI:10.1021/jacs.6b04550.
The dynamic nature of intrinsically disordered peptides makes them a challenge to characterize by solution-phase techniques. In order to gain insight into the relation between the disordered state and the environment, we explore the conformational space of the N-terminal 1-5 fragment of bradykinin (BK[1-5](2+)) in the gas phase by combining drift tube ion mobility, cold-ion spectroscopy, and first-principles simulations. The ion-mobility distribution of BK[1-5](2+) consists of two well-separated peaks. We demonstrate that the conformations within the peak with larger cross-section are kinetically trapped, while the more compact peak contains low-energy structures. This is a result of cis-trans isomerization of the two prolyl-peptide bonds in BK[1-5](2+). Density-functional theory calculations reveal that the compact structures have two very different geometries with cis-trans and trans-cis backbone conformations. Using the experimental CCSs to guide the conformational search, we find that the kinetically trapped species have a trans-trans configuration. This is consistent with NMR measurements performed in a solution, which show that 82% of the molecules adopt a trans-trans configuration and behave as a random coil.
Mapping the interaction of Bradykinin 1-5 with the exodomain of human protease activated receptor 4
FEBS Lett 2005 Jan 3;579(1):25-9.PMID:15620686DOI:10.1016/j.febslet.2004.11.041.
The angiotensin converting enzyme breakdown product of bradykinin, Bradykinin 1-5 (RPPGF), inhibits thrombin-induced human or mouse platelet aggregation. RPPGF binds to the exodomain of human protease-activated receptor 1 (PAR1). Studies determined if RPPGF also binds to the exodomain of human PAR4. RPPGF binds to a peptide of the thrombin cleavage site on PAR4. Recombinant wild-type and mutated exodomain of human PAR4 was prepared. The N-terminal arginine on RPPGF binds to the P2 position or proline46 on PAR4 to block thrombin cleavage. These data indicate that RPPGF influences thrombin activity by binding to the thrombin cleavage site on both PAR4 and PAR1.
Sensitive mass spectrometric determination of kinin-kallikrein system peptides in light of COVID-19
Sci Rep 2021 Feb 4;11(1):3061.PMID:33542252DOI:10.1038/s41598-021-82191-7.
The outbreak of COVID-19 has raised interest in the kinin-kallikrein system. Viral blockade of the angiotensin-converting enzyme 2 impedes degradation of the active kinin des-Arg(9)-bradykinin, which thus increasingly activates bradykinin receptors known to promote inflammation, cough, and edema-symptoms that are commonly observed in COVID-19. However, lean and reliable investigation of the postulated alterations is currently hindered by non-specific peptide adsorption, lacking sensitivity, and cross-reactivity of applicable assays. Here, an LC-MS/MS method was established to determine the following kinins in respiratory lavage fluids: kallidin, bradykinin, des-Arg(10)-kallidin, des-Arg(9)-bradykinin, bradykinin 1-7, bradykinin 2-9 and Bradykinin 1-5. This method was fully validated according to regulatory bioanalytical guidelines of the European Medicine Agency and the US Food and Drug Administration and has a broad calibration curve range (up to a factor of 103), encompassing low quantification limits of 4.4-22.8 pg/mL (depending on the individual kinin). The application of the developed LC-MS/MS method to nasal lavage fluid allowed for the rapid (~ 2 h), comprehensive and low-volume (100 µL) determination of kinins. Hence, this novel assay may support current efforts to investigate the pathophysiology of COVID-19, but can also be extended to other diseases.
Targeted LC-MS/MS platform for the comprehensive determination of peptides in the kallikrein-kinin system
Anal Bioanal Chem 2021 May;413(11):2971-2984.PMID:33693976DOI:10.1007/s00216-021-03231-9.
The kallikrein-kinin system (KKS) is involved in many physiological and pathophysiological processes and is assumed to be connected to the development of clinical symptoms of angioedema or COVID-19, among other diseases. However, despite its diverse role in the regulation of physiological and pathophysiological functions, knowledge about the KKS in vivo remains limited. The short half-lives of kinins, their low abundance and structural similarities and the artificial generation of the kinin bradykinin greatly hinder reliable and accurate determination of kinin levels in plasma. To address these issues, a sensitive LC-MS/MS platform for the comprehensive and simultaneous determination of the four active kinins bradykinin, kallidin, des-Arg(9)-bradykinin and des-Arg(10)-kallidin and their major metabolites bradykinin 2-9, bradykinin 1-7 and Bradykinin 1-5 was developed. This platform was validated according to the bioanalytical guideline of the US Food and Drug Administration regarding linearity, accuracy, precision, sensitivity, carry-over, recovery, parallelism, matrix effects and stability in plasma of healthy volunteers. The validated platform encompassed a broad calibration curve range from 2.0-15.3 pg/mL (depending on the kinin) up to 1000 pg/mL, covering the expected concentrations in disease states. No source-dependent matrix effects were identified, and suitable stability of the analytes in plasma was observed. The applicability of the developed platform was proven by the determination of endogenous levels in healthy volunteers, whose plasma kinin levels were successfully detected in the low pg/mL range. The established platform facilitates the investigation of kinin-mediated diseases (e.g. angioedema, COVID-19) and enables the assessment of the impact of altered enzyme activities on the formation or degradation of kinins.