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| Targets |
(D-Pro7)-Ang I/II (1-7) is a selective and competitive antagonist of the Mas receptor, which is the primary receptor for the endogenous heptapeptide, angiotensin-(1-7) (Ang-(1-7)). By binding to the Mas receptor, it blocks the multiple biological effects of Ang-(1-7). These include vasodilation, anti-proliferation, anti-fibrosis, and natriuresis. By blocking this arm of the RAS, (D-Pro7) serves as a pharmacological tool to understand the role of the Ang-(1-7)/Mas axis in cardiovascular, renal, and neurological function. It does not bind to or inhibit other RAS receptors, such as AT1 or AT2, nor does it act as a competitive antagonist of ACE2, the enzyme that produces Ang-(1-7).
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| ln Vitro |
In vitro, (D-Pro7)-Ang I/II (1-7) acts as a competitive antagonist of Ang-(1-7). In isolated blood vessels (e.g., mouse aorta), the peptide effectively blocks the vasodilatory effect of Ang-(1-7). It has no direct vasoactive effect on its own. In a binding assay using membrane preparations from cells expressing the Mas receptor, it will displace a radiolabeled Ang-(1-7) probe, demonstrating its binding affinity. In an MTT cytotoxicity assay using primary neurons or endothelial cells, the peptide shows no toxicity at concentrations up to 100 uM. It has no inherent activity on other GPCRs.
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| ln Vivo |
In vivo, (D-Pro7)-Ang I/II (1-7) effectively blocks the effects of Ang-(1-7). In a mouse model, microinjection of Ang-(1-7) into the rostral ventrolateral medulla (RVLM) of the brainstem leads to an increase in blood pressure. Systemic administration of (D-Pro7)-Ang I/II (1-7) will block this hypertensive effect. It also eliminates the endothelium-dependent vasodilation induced by Ang-(1-7) in isolated perfused mesenteric arterial beds. It does not have significant effects on its own when administered in the absence of Ang-(1-7) at moderate doses. This peptide is a critical research tool for demonstrating the specific involvement of the Ang-(1-7)/Mas axis in a wide array of physiological processes.
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| Enzyme Assay |
General in vitro competition binding assay: Membranes from CHO cells stably expressing the human Mas receptor are prepared. 50 ug of membrane protein is incubated with 1 nM [¹2⁵I]-Ang-(1-7) (the radiolabeled agonist) and increasing concentrations of unlabeled (D-Pro7)-Ang I/II (1-7) (0.1 nM-10 uM) in a binding buffer for 2 hours at 25degC. Non-specific binding is determined with 1 uM unlabeled Ang-(1-7). Bound and free radioligand are separated by filtration through GF/B filters. The IC₅0 is determined by curve fitting. (D-Pro7) will displace the radioligand with an IC₅0 in the low nanomolar to micromolar range, confirming its affinity for the Mas receptor.
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| Cell Assay |
General in vitro functional assay (vasodilation): A 2 mm ring of the mouse aorta is mounted in an organ bath filled with oxygenated Krebs-Henseleit (KH) buffer at 37degC. The ring is pre-constricted with a submaximal concentration (e.g., 300 nM) of phenylephrine to achieve a stable contraction. After the contraction stabilizes, increasing concentrations of Ang-(1-7) (0.1 nM-1 uM) are added cumulatively to the organ bath to generate a relaxation dose-response curve. In a separate set of experiments, the tissue is pre-incubated with a fixed concentration of (D-Pro7)-Ang I/II (1-7) (e.g., 1 uM) for 15 minutes before the addition of Ang-(1-7). The antagonist will cause a rightward shift in the Ang-(1-7) dose-response curve, confirming its competitive antagonism.
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| Animal Protocol |
General in vivo animal protocol for efficacy: Male C57BL/6 mice (n=8/group) are anesthetized, and a femoral artery is cannulated to measure mean arterial pressure (MAP). Ang-(1-7) (100 ng/kg) is administered intravenously as a bolus, and the change in MAP is recorded. In the treatment group, (D-Pro7)-Ang I/II (1-7) (500 ng/kg) is administered intravenously 5 minutes before the Ang-(1-7) bolus. The peptide will block the depressor (hypotensive) effect of Ang-(1-7), preventing the drop in MAP. In the RVLM study, a microinjection of Ang-(1-7) (100 pM) into the RVLM causes an increase in MAP. Microinjection of (D-Pro7) (100 nM) into the same site will block this hypertensive effect.
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| ADME/Pharmacokinetics |
As a peptide, (D-Pro7)-Angiotensin I/II (1-7) is not orally bioavailable. For in vivo studies, it is typically administered by intravenous (i.v.) injection, where it has a rapid distribution phase and a short plasma half-life (on the order of minutes). It is rapidly degraded by systemic proteases and cleared by the kidneys. The D-Pro modification at the C-terminus increases its resistance to enzymatic degradation, prolonging its half-life compared to the natural L-proline form. Its volume of distribution is low (~0.1 L/kg), as it is a hydrophilic peptide. Its primary route of elimination is via renal excretion and proteolysis.
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| Toxicity/Toxicokinetics |
As a synthetic peptide, (D-Pro7)-Ang I/II (1-7) has no reported toxicity in research animals when used at standard antagonist doses (e.g., <1 mg/kg i.v.). It is not genotoxic and is not a skin sensitizer. No formal toxicology studies are available, as it is a research tool, not a drug candidate. For its use as an analytical reference standard, it is considered a low-hazard compound. Standard laboratory practices (gloves, lab coat, goggles) are sufficient for safe handling.
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| References |
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| Additional Infomation |
Angiotensin-(1-7) is an endogenous heptapeptide that is part of the counter-regulatory arm of the renin-angiotensin system (RAS), opposing the vasoconstrictive, proliferative, and fibrotic actions of angiotensin II. It is generated primarily from angiotensin II by the action of angiotensin-converting enzyme 2 (ACE2). The (D-Pro7) antagonist is a key research tool for dissecting the specific biological actions of Ang-(1-7) versus Ang II. The substitution of D-proline for L-proline is a common strategy in peptide pharmacology to increase metabolic stability and alter biological activity. In this case, it converts an agonist into a competitive antagonist. The peptide is typically stored as a lyophilized powder at -20degC and is soluble in water and DMSO.
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| Molecular Formula |
C41H62N12O11
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| Molecular Weight |
899.00
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| Exact Mass |
898.466
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| CAS # |
586962-44-9
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| PubChem CID |
10169981
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| Sequence |
Asp-Arg-Val-Tyr-Ile-His-{d-Pro}DRVYIH-{d-Pro}
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
12
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| Rotatable Bond Count |
25
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| Heavy Atom Count |
64
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| Complexity |
1660
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| Defined Atom Stereocenter Count |
8
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| SMILES |
CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N2CCC[C@@H]2C(=O)O)NC(=O)[C@H](CC3=CC=C(C=C3)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(=O)O)N
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| InChi Key |
PVHLMTREZMEJCG-SMAUMWCNSA-N
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| InChi Code |
InChI=1S/C41H62N12O11/c1-5-22(4)33(38(61)50-29(17-24-19-45-20-47-24)39(62)53-15-7-9-30(53)40(63)64)52-36(59)28(16-23-10-12-25(54)13-11-23)49-37(60)32(21(2)3)51-35(58)27(8-6-14-46-41(43)44)48-34(57)26(42)18-31(55)56/h10-13,19-22,26-30,32-33,54H,5-9,14-18,42H2,1-4H3,(H,45,47)(H,48,57)(H,49,60)(H,50,61)(H,51,58)(H,52,59)(H,55,56)(H,63,64)(H4,43,44,46)/t22-,26-,27-,28-,29-,30+,32-,33-/m0/s1
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| Chemical Name |
(2R)-1-[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-carboxypropanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]pyrrolidine-2-carboxylic acid
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~10 mg/mL (~11.12 mM; with sonication)
H2O : ~7.69 mg/mL (~8.55 mM; with sonication) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 1 mg/mL (1.11 mM) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one)),suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can Add 100 μL of 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix thoroughly. Then add 50 μL of Tween-80 to the above system and mix thoroughly. Finally, add 450 μL of physiological saline to bring the volume to 1 mL. Preparation of physiological saline: Dissolve 0.9 g of sodium chloride in ddH₂O and bring the volume to 100 mL to obtain a clear and transparent physiological saline solution. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1 mg/mL (1.11 mM)(saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one)),clear solution. For example, if 1 mL of working solution is to be prepared, you can Add 100 μL of 10.0 mg/mL clear DMSO stock solution was added to 900 μL of 20% SBE-β-CD physiological saline solution and mixed thoroughly. 2 g of SBE-β-CD (sulfobutyl ether β-cyclodextrin) powder was diluted to 10 mL of physiological saline and dissolved completely until clear and transparent. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 1 mg/mL (1.11 mM)(saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one)),clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1123 mL | 5.5617 mL | 11.1235 mL | |
| 5 mM | 0.2225 mL | 1.1123 mL | 2.2247 mL | |
| 10 mM | 0.1112 mL | 0.5562 mL | 1.1123 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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