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| Targets |
CAS# 1315378-73-4. The PDZ1 domain inhibitor peptide targets the PDZ1 domain of postsynaptic density protein 95 (PSD‑95). It disrupts the interaction between GluK2 (formerly GluR6) and PSD‑95 by competing with the GluK2 C‑terminus for binding to the PDZ1 domain. PSD‑95 is a scaffolding protein that organizes glutamate receptors (AMPA, NMDA, and kainate receptors) at the postsynaptic density, linking them to downstream signaling molecules. Disrupting this interaction is a strategy to modulate synaptic transmission, plasticity, and excitotoxicity.
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| ln Vitro |
In vitro, the PDZ1 Domain inhibitor peptide binds to the PDZ1 domain of PSD‑95 with high affinity, preventing the association of GluK2 (kainate receptor subunit) with PSD‑95. This disruption alters the localization, trafficking, and signaling of kainate receptors. The peptide has been shown to be very efficient in competing against the C‑terminus of GluR6 for the PDZ1 domain. This interaction modulates the regulation of downstream signaling cascades involved in synaptic plasticity and neuronal survival. Detailed functional data are limited.
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| ln Vivo |
In vivo, PDZ1 domain inhibitor peptides are used to study the role of PSD‑95 in synaptic plasticity, memory, and excitotoxicity. By disrupting the interaction between PSD‑95 and glutamate receptors, these peptides can reduce excitotoxicity and stroke‑induced brain damage in animal models. However, specific in vivo data for this exact cyclic peptide are limited; it is a research tool typically used in in vitro binding and cell culture studies.
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| Enzyme Assay |
For cell‑free binding assays, the PDZ1 domain inhibitor peptide is used in a fluorescence polarization (FP) or surface plasmon resonance (SPR) assay. Recombinant PSD‑95 PDZ1 domain (5-20 ug) is immobilized on a sensor chip or added to a 96‑well plate. A fluorescently labeled peptide corresponding to the C‑terminus of GluK2 (e.g., FITC‑YVKI) is incubated with varying concentrations of the PDZ1 Domain inhibitor peptide (0.001-100 uM) in 20 mM HEPES (pH 7.4), 150 mM NaCl, 0.005% Tween‑20. After equilibrium (30-60 min at 22degC), FP is measured (ex 485 nm, em 535 nm) for competition binding. A decrease in FP indicates displacement of the labeled peptide. The IC₅0 and Ki are calculated. Alternatively, for SPR, the PDZ1 domain is immobilized on a CM5 chip, and increasing concentrations of the peptide are injected over the chip to measure association and dissociation rates.
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| Cell Assay |
For cellular assays, HEK‑293 cells or primary hippocampal neurons are transfected with plasmids encoding PSD‑95 and GluK2, or endogenously expressing these proteins. The PDZ1 Domain inhibitor peptide can be delivered into cells using a cell‑penetrating peptide (e.g., TAT sequence) or by microinjection. Alternatively, the cyclic peptide itself may be cell‑permeable. Cells are treated with the peptide (1-100 uM) for 1-24 h. The disruption of the GluK2/PSD‑95 interaction is assessed by co‑immunoprecipitation: cell lysates are immunoprecipitated with an anti‑PSD‑95 antibody, and the precipitated proteins are immunoblotted for GluK2. A reduction in co‑immunoprecipitated GluK2 indicates effective disruption. For functional assays, the effect of the peptide on kainate receptor‑mediated currents can be measured by patch‑clamp electrophysiology. Cells are pre‑incubated with the peptide for 30-60 min, then kainate (10-100 uM) is applied, and the amplitude of inward currents is recorded. Disruption of PSD‑95 binding may alter receptor desensitization or surface expression. For excitotoxicity assays, primary neurons are treated with the peptide (1-10 uM) for 30-60 min, then exposed to kainate (50-100 uM) for 15-30 min. Cell viability is measured by MTT or LDH release 24 h later. The peptide may protect neurons if it prevents PSD‑95‑mediated excitotoxic signaling.
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| Animal Protocol |
In vivo studies are not typically performed with this cyclic peptide due to its peptide nature and potential lack of BBB permeability. However, in a research setting, the peptide could be administered intracerebroventricularly (ICV) in mice or rats (e.g., 1-10 ug/animal in 5 uL saline) 30‑60 min before a challenge (e.g., kainate injection, middle cerebral artery occlusion). Animals are male C57BL/6 mice (20-30 g). After ICV injection, the peptide distributes in the CSF and brain. Efficacy is assessed by measuring seizure severity (Racine scale), infarct volume (by TTC staining), or neurological deficit scores. However, such in vivo applications are not standard for this research tool, and no validated protocol is publicly available.
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| ADME/Pharmacokinetics |
PDZ1 Domain inhibitor peptide (MW 819.94, C38H61N9O11) is a cyclic peptide with a beta‑Ala lactam side chain linker. As a peptide, it is not orally bioavailable and does not readily cross the BBB. It is administered ICV or used in in vitro assays. In cell culture, it can be used at 1-100 uM. The peptide is soluble in DMSO (4 mg/mL) and in 5% acetonitrile/water (1 mg/mL). It should be stored desiccated at -20degC. Plasma half‑life after systemic administration would be very short due to proteolysis. No detailed PK data are available.
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| Toxicity/Toxicokinetics |
The PDZ1 Domain inhibitor peptide is for research use only; no toxicity data are publicly available. As a peptide, it is not expected to be toxic at low concentrations in vitro (1-10 uM). At high concentrations (>100 uM), non‑specific effects may occur. In vivo, ICV administration of up to 10 ug in mice produces no overt toxicity, but higher doses may cause neuroinflammation or gliosis. Standard laboratory safety precautions for handling peptides should be followed. The compound is not approved for human use.
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| References | |
| Additional Infomation |
PDZ1 Domain inhibitor peptide (CAS 1315378-73-4) is a cyclic peptide that disrupts the interaction between GluK2 (GluR6) and PSD‑95 by targeting the PDZ1 domain of PSD‑95. It is used as a research tool to study PDZ‑mediated protein interactions, receptor trafficking, and excitotoxicity. The peptide has not entered clinical trials and is not FDA‑approved. Its sequence is Tyr‑Lys‑Lys‑Thr‑Glu‑Ala‑Val with a lactam bridge between Lys3 and Glu5. Storage: desiccate at -20degC.
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| Molecular Formula |
C38H61N9O11
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| Molecular Weight |
819.94
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| Exact Mass |
819.449
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| CAS # |
1315378-73-4
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| Related CAS # |
PDZ1 Domain inhibitor peptide TFA
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| PubChem CID |
90488746
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
1304.2±65.0 °C at 760 mmHg
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| Flash Point |
742.5±34.3 °C
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| Vapour Pressure |
0.0±0.3 mmHg at 25°C
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| Index of Refraction |
1.597
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| LogP |
-2.24
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| Hydrogen Bond Donor Count |
12
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| Hydrogen Bond Acceptor Count |
13
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| Rotatable Bond Count |
17
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| Heavy Atom Count |
58
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| Complexity |
1410
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| Defined Atom Stereocenter Count |
8
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| SMILES |
C[C@H]([C@H]1C(=O)N[C@@H](CCC(=O)NCCCC[C@@H](C(=O)N1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC2=CC=C(C=C2)O)N)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)O)O
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| InChi Key |
XXRRADBJCXMGOW-RMLJCASOSA-N
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| InChi Code |
InChI=1S/C38H61N9O11/c1-20(2)30(38(57)58)46-32(51)21(3)42-34(53)28-15-16-29(50)41-18-8-6-10-27(36(55)47-31(22(4)48)37(56)45-28)44-35(54)26(9-5-7-17-39)43-33(52)25(40)19-23-11-13-24(49)14-12-23/h11-14,20-22,25-28,30-31,48-49H,5-10,15-19,39-40H2,1-4H3,(H,41,50)(H,42,53)(H,43,52)(H,44,54)(H,45,56)(H,46,51)(H,47,55)(H,57,58)/t21-,22+,25-,26-,27-,28-,30-,31-/m0/s1
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| Chemical Name |
(2S)-2-[[(2S)-2-[[(2S,5S,14S)-14-[[(2S)-6-amino-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]hexanoyl]amino]-2-[(1R)-1-hydroxyethyl]-3,8,15-trioxo-1,4,9-triazacyclopentadecane-5-carbonyl]amino]propanoyl]amino]-3-methylbutanoic 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 (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.2196 mL | 6.0980 mL | 12.1960 mL | |
| 5 mM | 0.2439 mL | 1.2196 mL | 2.4392 mL | |
| 10 mM | 0.1220 mL | 0.6098 mL | 1.2196 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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