Pep 2-8 (Synonyms: TVFTSWEEYLDWV-NH2) |
Catalog No.GC50447
One-Click Copy Product Info
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Pep 2-8, a linear peptide consisting of 13 amino acids, inhibits PCSK9 with a KD value of 0.7μM and suppresses the binding of LDL receptors and the EGF(A) domain to PCSK9, with IC50 values of 0.8 and 0.4μM, respectively.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1541011-97-5
Sample solution is provided at 25 µL, 10mM.
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Pep 2-8, a linear peptide consisting of 13 amino acids, inhibits PCSK9 with a KD value of 0.7μM and suppresses the binding of LDL receptors and the EGF(A) domain to PCSK9, with IC50 values of 0.8 and 0.4μM, respectively [1]. Pep 2-8 neutralizes the activity of PCSK9, prevents the degradation of LDL receptors and restore the function of LDL receptors in cells[2]. Pep 2-8 has been widely used as a model compound to develop a series of derivatives for regulating the level of LDLR protein in cells [3].
In vitro, Pep 2-8 treatment for 24h (10µM) in the presence of lipopolysaccharide (20ng/mL;24h) significantly decreased phosphorylation of mTOR in vascular smooth muscle cells (VSMCs) and decreased apoptosis[4]. Pep 2-8 (10μM) pretreatment of VSMCs from obese insulin-resistant Zucker rats for 30 minutes can inhibit the expression of pERK-1/2 induced by a high glucose environment, and block the activation of the MAPK/ERK-1/2 pathway[5].
In vivo, Pep 2-8 treatment via subcutaneous injection (10µg/kg) once every two weeks for 10 weeks significantly inhibited the downregulation of NOX4, MAPK subunits, and NF-κB expression caused by PCSK9 in the aorta of mice, as well as the secretion of pro-inflammatory cytokines, preventing vascular aging[6]. A single intravenous injection of Pep 2-8 (10μg/kg) for 120 minutes reduced the myocardial infarction area in rats with ischemia/reperfusion injury, improved the mitochondrial function of the heart, and decreased the expression of apoptosis-related proteins[7]. Intravenous injection of Pep 2-8 (10µg per mouse/day) for one week improved the contractile function of the hearts of mice with left coronary artery (LCA) occlusion and inhibited the autophagic activity in ischemic hearts[8].
References:
[1] Zhang Y, Eigenbrot C, Zhou L, et al. Identification of a small peptide that inhibits PCSK9 protein binding to the low density lipoprotein receptor[J]. Journal of Biological Chemistry, 2014, 289(2): 942-955.
[2] Lammi C, Sgrignani J, Arnoldi A, et al. Biological characterization of computationally designed analogs of peptide TVFTSWEEYLDWV (Pep2-8) with increased PCSK9 antagonistic activity[J]. Scientific reports, 2019, 9(1): 2343.
[3] Tombling B J, Lammi C, Bollati C, et al. Increased valency improves inhibitory activity of peptides targeting proprotein convertase subtilisin/kexin type 9 (PCSK9)[J]. ChemBioChem, 2021, 22(12): 2154-2160.
[4] Ding Z, Liu S, Wang X, et al. Cross-talk between PCSK9 and damaged mtDNA in vascular smooth muscle cells: role in apoptosis[J]. Antioxidants & redox signaling, 2016, 25(18): 997-1008.
[5] Barale C, Tempesta G, Melchionda E, et al. PCSK9 Expression in Vascular Smooth Muscle Cells: Role of Insulin Resistance and High Glucose[J]. International Journal of Molecular Sciences, 2025, 26(3): 1003.
[6] Liu S, Wu J, Stolarz A, et al. PCSK9 attenuates efferocytosis in endothelial cells and promotes vascular aging[J]. Theranostics, 2023, 13(9): 2914.
[7] Palee S, McSweeney C M, Maneechote C, et al. PCSK9 inhibitor improves cardiac function and reduces infarct size in rats with ischaemia/reperfusion injury: Benefits beyond lipid‐lowering effects[J]. Journal of cellular and molecular medicine, 2019, 23(11): 7310-7319.
[8] Ding Z, Wang X, Liu S, et al. PCSK9 expression in the ischaemic heart and its relationship to infarct size, cardiac function, and development of autophagy[J]. Cardiovascular Research, 2018, 114(13): 1738-1751.
| Cell experiment [1]: | |
Cell lines | HepG2 cells |
Preparation Method | HepG2 cells were seeded at a density of 3×104 cells per well in a 96-well plate. After 24 hours, the culture medium was replaced with DMEM medium containing 10% lipoprotein-deficient serum. Different concentrations of Pep 2-8(1.5, 3.0, 6.0, 12.5, 25, 50, 100, and 200μM) were pre-incubated with 15μg/ml PCSK9 (dissolved in 0.5% DMSO) for 30 minutes, and then added to the cells. After 1.5 hours, 10μg/ml BODIPY-LDL was added and incubated for 3.5 hours. The cells were washed three times with PBS and the fluorescence was measured on a microplate reader. |
Reaction Conditions | 1.5, 3.0, 6.0, 12.5, 25, 50, 100, and 200μM; 4h |
Applications | Pep 2-8 treatment significantly restored LDL uptake in HepG2 cells. |
| Animal experiment [2]: | |
Animal models | Male C57BL/6 mice |
Preparation Method | Male C57BL/6 mice were raised under standard conditions. Before reaching 24 months of age, they were subcutaneously injected with the Pep 2-8 (10µg/kg dissolved in 100µL normal saline) or 100µL normal saline every 2 weeks for a total of 10 weeks (10 mice in each group). After injecting Pep 2-8, the mice were monitored daily. At 24-month endpoint, after euthanizing the mice by CO2 asphyxiation, the aorta samples were dissected for further molecular and immunohistochemical analyses. |
Dosage form | 10µg/kg every 2 weeks for 10 weeks; s.c. |
Applications | Pep 2-8 treatment downregulated the expressions of the aging markers pro-IL-1β, NF-κB and p22phox in the aortic arch of mice. |
References: | |
| Cas No. | 1541011-97-5 | SDF | |
| Synonyms | TVFTSWEEYLDWV-NH2 | ||
| Formula | C83H110N16O24 | M.Wt | 1715.88 |
| Solubility | Soluble 2mg/mL in PBS (pH 7.4) | Storage | store at -20°C, protect from light |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 582.8 μL | 2.914 mL | 5.8279 mL |
| 5 mM | 116.6 μL | 582.8 μL | 1.1656 mL |
| 10 mM | 58.3 μL | 291.4 μL | 582.8 μL |
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Quality Control & SDS
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- Purity: >99.00% Appearance: A solid
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- SDS (Safety Data Sheet)
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Average Rating: 5 (Based on Reviews and 8 reference(s) in Google Scholar.)