| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
NSF/GluR2 interactions[1]
Pep2m targets the NSF-binding domain of the AMPA receptor subunit GluA2. By blocking the NSF-GluA2 interaction, this peptide prevents the recycling and surface expression of GluA2-containing AMPA receptors. This mechanism specifically modulates GluA2-containing AMPAR activity without directly affecting NMDA receptors, making it a valuable tool for studying subunit-specific AMPA receptor functions. |
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| ln Vitro |
Pep2m, myristoylated TFA (10 μM), inhibits AMPA receptor (AMPAR) potentiation mediated by PKMζ[1]. Myristoylated TFA, Pep2m, and LTP maintenance do not prevent the rise of PKMζ in hippocampus slices, suggesting that preventing NSF/GluR2 connections does not stop PKMζ synthesis from being induced[1]. Pep2m, myristoylated TFA, reverses persistent potentiation at both weakly stimulated and powerfully stimulated synapses that undergo synaptic tagging and capture, and prevents NSF/GluR2-mediated AMPAR trafficking [1].
In hippocampal neurons, viral expression of Pep2m reduces the surface expression of AMPA receptors while leaving NMDA receptor surface expression unchanged. The peptide completely occludes long-term depression (LTD) expression at calcium-impermeable AMPAR synapses but not at calcium-permeable AMPAR synapses, confirming that CI-AMPAR LTD involves postsynaptic AMPAR trafficking. Pep2m also decreases the concentration of GluA2 in the presynaptic active zone membrane. |
| ln Vivo |
In the formalin test, paw withdrawal thresholds (PWTs) on nociceptive responses increase in response to Pep2m, myristoylated TFA (10 µg/20 µL)[2].
Infusion of myristoylated Pep2m into the nucleus accumbens core (AcbC) of male C57BL/6J mice reduces ethanol-reinforced responding without affecting sucrose-only self-administration or motor activity. Expression of Pep2m from a neuronal-specific adenoviral system provides significant neuroprotection to primary CA1-CA3 hippocampal neurons following kainate stimulation, accompanied by a reduction in Ca2+ influx. In hippocampal slices, intracellular application of Pep2m reduces apical spine responses and increases paired-pulse facilitation. |
| Enzyme Assay |
In binding assays, the interaction between GluA2 and NSF is assessed using GST pull-down or co-immunoprecipitation methods. Recombinant GST-fused NSF protein is immobilized on glutathione-agarose beads and incubated with cell lysates containing GluA2 in the presence or absence of Myr-Pep2m TFA (1-50 uM). After washing, bound proteins are eluted and analyzed by SDS-PAGE and Western blotting with anti-GluA2 antibodies to quantify the degree of disruption of the NSF-GluA2 interaction.
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| Cell Assay |
Primary hippocampal neurons are cultured and transfected with Pep2m-expressing adenoviral vectors or treated with myristoylated Pep2m peptide (1-10 uM) for 24-48 hours. Surface AMPA receptor expression is assessed by biotinylation assays followed by Western blotting. For electrophysiological recordings, whole-cell patch clamp is performed and Pep2m (100-500 uM) is included in the internal pipette solution to assess effects on AMPAR-mediated synaptic transmission and plasticity.
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| Animal Protocol |
Animal/Disease Models: Female and male Long-Evans hooded rats (8 weeks)[2 ]
Doses: 10 µg (in 20 µL) Route of Administration: Intrathecal injection Experimental Results: Resulted in an increase in PWTs, in both male and female rats at various time points tested. In male C57BL/6J mice, mice are surgically implanted with bilateral guide cannulas targeting the nucleus accumbens core. After recovery, Myr-Pep2m (dissolved in artificial cerebrospinal fluid) is infused (0.5 uL/side, concentration not specified, likely 1-10 mM) 10 minutes before operant self-administration sessions. For ischemia studies, a neuronal-specific adenoviral system expressing Pep2m is injected into the CA1-CA3 region of the hippocampus. Seven days later, mice receive kainate injections and neuronal survival is assessed by Nissl staining. |
| ADME/Pharmacokinetics |
As a myristoylated peptide, Myr-Pep2m TFA is cell-permeable but suffers from short in vivo half-life due to rapid proteolytic degradation in serum. Detailed quantitative pharmacokinetic parameters (e.g., t½, Cmax, AUC, CL) are not available in the literature. Dosage for in vivo infusion is typically empirically determined based on the desired degree of GluA2/NSF disruption. Peptide solutions should be freshly prepared and used immediately.
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| Toxicity/Toxicokinetics |
No systematic toxicity studies have been reported for Myr-Pep2m TFA. The compound has been safely used in rodents without reports of overt behavioral or physiological toxicity at the dosages required for experimental efficacy. Myristoylated peptides generally exhibit low immunogenicity, but long-term toxicity data are not available. Standard laboratory safety precautions for peptide handling should be followed.
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| References |
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| Additional Infomation |
Pep2m is a research-grade inhibitor and has not been approved for clinical use. It is one of several widely utilized peptides that target AMPA receptor trafficking, including pepR845A and TAT-pep2m. It serves as an invaluable experimental tool to investigate the NSF-dependent regulation of AMPARs in synaptic plasticity, learning, memory, and drug addiction. The TFA salt counterion improves solubility and handling in aqueous buffers, while the myristoyl group (C14:0, a saturated fatty acid) facilitates non-endocytic membrane translocation.
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| Molecular Formula |
C65H119F3N18O16S
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| Molecular Weight |
1497.83
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| Related CAS # |
Pep2m, myristoylated;1423381-07-0
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| Appearance |
White to off-white solid powder
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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) |
DMSO :~33.33 mg/mL (~22.25 mM)
H2O :~3.33 mg/mL (~2.22 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (1.67 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 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (1.67 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.6676 mL | 3.3382 mL | 6.6763 mL | |
| 5 mM | 0.1335 mL | 0.6676 mL | 1.3353 mL | |
| 10 mM | 0.0668 mL | 0.3338 mL | 0.6676 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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