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| Targets |
PrP (106-126) exerts its neurotoxic effects through interaction with the cellular prion protein (PrPC). Synthetic peptide homologous to region 106-126 of the prion protein is toxic to cells expressing PrPC, but not to PrP knockout neurons, arguing for a specific role of PrPC in mediating the peptide‘s activity. The peptide induces microglial activation, production of reactive oxygen species (ROS), and activation of apoptotic pathways in neurons. It also interacts with cell membranes, forming ion channels and disrupting membrane integrity. Additionally, PrP (106-126) can bind to laminin and other extracellular matrix components, contributing to its pathological effects. The neurotoxicity is dependent on the peptide's ability to form beta-sheet-rich fibrillar aggregates.
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| ln Vitro |
In N2a cells, PrP (106–126) (100 μM) gradually causes mTOR phosphorylation. The production of ROS is substantially higher in cells treated with PrP (106–126) than in control cells treated with PBS. Apoptosis elicited by PrP (106–126) is enhanced by PRAS40 knockdown. By activating mTOR and AKT, PRAS40 reduces the neuronal apoptosis caused by PrP (106–126)[1]. PrP (106–126) preferentially interacts with PBECs via their luminal side, resulting in cumulative cell death as demonstrated by the release of lactate dehydrogenase, decrease of 3-(4,5-dimethylthiazol-2-yl)–2,5-diphenyltetrazolium bromide, induction of Caspase 3 and direct cell counting. Furthermore, while the PBEC maintained confluency, PrP (106–126) but not its corresponding scrambled peptide causes a 50% decrease in trans-endothelial electrical resistance[2].
In vitro, PrP (106-126) is toxic to primary neurons and neuronal cell lines (e.g., GT1-7, SH-SY5Y, PC12). Treatment of neurons with 10-100 microM PrP (106-126) for 24-72 hours induces cell death characterized by apoptosis (caspase-3 activation, DNA fragmentation) and/or necrosis. The peptide induces microglial activation, leading to the production of pro-inflammatory cytokines (IL-1beta, TNF-alpha) and neurotoxic factors. PrP (106-126) also induces oxidative stress, as measured by increased ROS production, lipid peroxidation, and reduced glutathione levels. The peptide forms amyloid-like fibrils in vitro, as assessed by Thioflavin T fluorescence and transmission electron microscopy (TEM). The fibrillogenic and neurotoxic properties are dependent on specific amino acid residues, particularly the hydrophobic region at the C-terminus (AVVGGLG). The control peptide, PrP (106-126) scrambled, is generally non-toxic. |
| ln Vivo |
In vivo, PrP (106-126) has been used to study prion-like neurotoxicity in animal models. Intracerebral injection of the peptide into the brains of wild-type mice (but not PrP knockout mice) induces neuronal loss, astrocytosis, and microglial activation, mimicking some aspects of prion disease pathology. Injection of PrP (106-126) into the hippocampus results in learning and memory deficits in behavioral tests (e.g., Morris water maze). The peptide also induces apoptosis and spongiform degeneration in some models, though the extent depends on the dose, route of administration, and mouse strain. Amidation and structure relaxation have been shown to abolish the neurotoxicity of PrP (106-126) in vivo and in vitro, highlighting the importance of the peptide‘s structure for its pathogenic activity.
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| Enzyme Assay |
A typical non-cellular (cell-free) protocol for evaluating the amyloid fibril formation of PrP (106-126) uses a Thioflavin T (ThT) fluorescence assay. PrP (106-126) is dissolved in hexafluoroisopropanol (HFIP) at 1 mM and incubated overnight to monomerize the peptide. The HFIP is then evaporated under nitrogen, and the peptide is resuspended in sterile water at 1 mM. For the fibrillation assay, the peptide is diluted to 50-100 microM in PBS (pH 7.4) or other buffers, and ThT is added to a final concentration of 10-20 microM. The mixture is incubated at 37degC with continuous shaking in a 96-well plate (black, clear bottom). Fluorescence intensity is measured at excitation/emission of 440/480 nm every 10-30 minutes for 2-72 hours using a microplate reader. Fibril formation is indicated by an increase in ThT fluorescence over time. The lag phase, elongation phase, and plateau phase of the fibrillation curve are analyzed. Transmission electron microscopy (TEM) is used to confirm the presence of fibrils at the end of the experiment.
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| Cell Assay |
A standard in vitro neurotoxicity protocol for PrP (106-126) uses primary cortical neurons isolated from embryonic day 16-18 (E16-18) mouse embryos. Cortices are dissected, dissociated with papain (20 U/mL) or trypsin (0.25%), and plated on poly-D-lysine-coated plates at 1-2×10⁵ cells/well in 96-well plates or 5×10⁵ cells/well in 24-well plates. Neurons are cultured in Neurobasal medium supplemented with B27 and GlutaMAX for 7-10 days in vitro (DIV) before use. The cultured neurons are treated with PrP (106-126) (10, 25, 50, 100 microM) for 24-72 hours. A mutant or scrambled peptide is used as a negative control. After treatment, cell viability is assessed by MTT reduction (10 microL of 5 mg/mL MTT per well for 4 hours at 37degC), LDH release assay (measured at 490 nm), or by quantifying apoptotic nuclei by Hoechst 33342 staining (pyknotic nuclei). Microglial activation can be studied in mixed neuron-glia cultures or by using BV-2 microglial cells treated with PrP (106-126) and measuring cytokine release (IL-1beta, TNF-alpha) by ELISA.
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| Animal Protocol |
An in vivo animal protocol for evaluating the neurotoxic effects of PrP (106-126) uses intracerebroventricular (ICV) or intrahippocampal injection in adult male C57BL/6 mice (8-10 weeks old). Mice are anesthetized with ketamine/xylazine and positioned in a stereotaxic frame. A 30-gauge needle is inserted into the lateral ventricle (ICV) or the hippocampus (coordinates: anterior-posterior -2.0 mm, medial-lateral +/-1.5 mm, dorsal-ventral -1.5 mm from bregma). PrP (106-126) is dissolved in sterile PBS at a concentration of 5-10 microg/microL, and 1-5 microL (5-50 microg total) is injected slowly (0.5 microL/min). Control animals receive an equal volume of vehicle (PBS) or a scrambled PrP peptide. After injection, the needle is left in place for 5 minutes before withdrawal. Animals are monitored for 1-14 days post-injection. Behavioral tests (e.g., Morris water maze, open field, Y-maze) are performed starting on day 7. At the end of the study, mice are perfused, brains are harvested, and sections are processed for histological analysis (H&E staining for neuronal loss, Iba-1 for microgliosis, GFAP for astrocytosis, and TUNEL staining for apoptosis). Alternatively, brains can be homogenized and analyzed for cytokine levels (IL-1beta, TNF-alpha) by ELISA.
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| ADME/Pharmacokinetics |
Peptides like PrP (106-126) are rapidly cleared from the central nervous system (CNS) when administered directly (intracerebroventricularly or intrahippocampally). The half-life in the brain is short (minutes to hours) due to proteolytic degradation by peptidases. Because the peptide is not a drug candidate but a research tool, detailed pharmacokinetic studies have not been performed. The peptide is unlikely to cross the blood-brain barrier (BBB) due to its hydrophilic nature and high molecular weight (approximately 2000 Da). When administered peripherally, it does not reach the brain in significant concentrations. Therefore, PrP (106-126) is almost always administered directly into the brain or cerebrospinal fluid (CSF) for in vivo studies.
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| Toxicity/Toxicokinetics |
PrP (106-126) is a synthetic peptide that is widely used as a model for prion-induced neurotoxicity. At concentrations used in vitro (10-100 microM) and in vivo (5-50 microg ICV), the peptide is neurotoxic and induces cell death in neurons. However, the peptide itself is not considered a therapeutic agent; it is a research tool used to model disease. Toxicity data are specifically related to its neurotoxic effects in experimental models. PrP (106-126) has no clinical utility and is strictly for research purposes. Standard laboratory safety precautions should be followed when handling the peptide, including the use of gloves and lab coats. The lyophilized peptide should be stored at -20degC, and working solutions should be prepared fresh to prevent aggregation. Avoid inhalation and ingestion. PrP (106-126) is for research use only and should not be used in humans or animals for therapeutic or diagnostic purposes.
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| References |
[1]. Yang W, et al. PRAS40 alleviates neurotoxic prion peptide-induced apoptosis via mTOR-AKT signaling. CNS Neurosci Ther. 2017 May;23(5):416-427.
[2]. Cooper I, et al. Interactions of the prion peptide (PrP 106-126) with brain capillary endothelial cells: coordinated cell killing and remodeling of intercellular junctions. J Neurochem. 2011 Feb;116(4):467-75 |
| Additional Infomation |
PrP (106-126) is a synthetic peptide corresponding to residues 106-126 of the human prion protein, with the amino acid sequence H-KTNMKHMAGAAAAAGAVVGGLG-OH. Its molecular formula is C85H142N28O27S, and its molecular weight is approximately 1960 g/mol. This peptide is a well-established model for studying the pathogenesis of prion diseases (transmissible spongiform encephalopathies) due to its ability to form amyloid fibrils, induce neurotoxicity, and activate microglia. It exhibits PrPC-dependent neurotoxicity both in vivo and in vitro and is used to screen for neuroprotective compounds. The peptide is for research use only and is not intended for therapeutic applications. It should be stored at -20degC, protected from light and moisture.
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| Molecular Formula |
C80H138N26O24S2
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| Molecular Weight |
1912.30
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| Exact Mass |
1910.98
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| CAS # |
148439-49-0
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| PubChem CID |
71312203
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
0.334
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| Hydrogen Bond Donor Count |
27
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| Hydrogen Bond Acceptor Count |
30
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| Rotatable Bond Count |
64
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| Heavy Atom Count |
132
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| Complexity |
3910
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| Defined Atom Stereocenter Count |
17
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| SMILES |
C(O)(=O)CNC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)CNC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC1N=CNC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H]([C@H](O)C)NC(=O)[C@H](CCCCN)N
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| InChi Key |
XPZWWTIIKSODDO-MBNDGZRNSA-N
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| InChi Code |
InChI=1S/C80H138N26O24S2/c1-38(2)28-53(72(122)90-36-61(113)114)98-60(112)33-86-57(109)32-89-78(128)62(39(3)4)105-79(129)63(40(5)6)104-70(120)44(10)93-59(111)35-87-65(115)41(7)94-68(118)45(11)96-69(119)46(12)95-67(117)43(9)92-58(110)34-88-66(116)42(8)97-73(123)51(22-26-131-14)100-76(126)54(29-48-31-85-37-91-48)102-74(124)50(21-17-19-25-82)99-75(125)52(23-27-132-15)101-77(127)55(30-56(84)108)103-80(130)64(47(13)107)106-71(121)49(83)20-16-18-24-81/h31,37-47,49-55,62-64,107H,16-30,32-36,81-83H2,1-15H3,(H2,84,108)(H,85,91)(H,86,109)(H,87,115)(H,88,116)(H,89,128)(H,90,122)(H,92,110)(H,93,111)(H,94,118)(H,95,117)(H,96,119)(H,97,123)(H,98,112)(H,99,125)(H,100,126)(H,101,127)(H,102,124)(H,103,130)(H,104,120)(H,105,129)(H,106,121)(H,113,114)/t41-,42-,43-,44-,45-,46-,47+,49-,50-,51-,52-,53-,54-,55-,62-,63-,64-/m0/s1
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| Chemical Name |
2-[[(2S)-2-[[2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S,3R)-2-[[(2S)-2,6-diaminohexanoyl]amino]-3-hydroxybutanoyl]amino]-4-oxobutanoyl]amino]-4-methylsulfanylbutanoyl]amino]hexanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-4-methylsulfanylbutanoyl]amino]propanoyl]amino]acetyl]amino]propanoyl]amino]propanoyl]amino]propanoyl]amino]propanoyl]amino]acetyl]amino]propanoyl]amino]-3-methylbutanoyl]amino]-3-methylbutanoyl]amino]acetyl]amino]acetyl]amino]-4-methylpentanoyl]amino]acetic 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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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) |
H2O: 1 mg/mL (0.52 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 100 mg/mL (52.29 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.5229 mL | 2.6147 mL | 5.2293 mL | |
| 5 mM | 0.1046 mL | 0.5229 mL | 1.0459 mL | |
| 10 mM | 0.0523 mL | 0.2615 mL | 0.5229 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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