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| 10mg |
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| Targets |
AMPAR[1]
AMPA receptors (AMPARs) via the GluA2 subunit. TAT-GluA2 3Y is an interference peptide that disrupts the interaction between the GluA2 subunit of AMPARs and the endocytic machinery (specifically, it may interfere with the binding of the GluA2 C‑terminus to proteins such as GRIP1, PICK1, or AP2). By blocking AMPAR endocytosis, the peptide prevents the loss of AMPARs from the synaptic membrane, which is a key mechanism for long‑term depression (LTD) at glutamatergic synapses. |
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| ln Vitro |
In vitro, TAT-GluA2 3Y (1‑10 uM) penetrates neurons via the Tat sequence and blocks the endocytosis of AMPARs. In hippocampal slice preparations, it prevents the induction of long‑term depression (LTD) elicited by low‑frequency stimulation (LFS) or by pharmacological agents (e.g., NMDA or mGluR agonists). It does not affect long‑term potentiation (LTP). In primary neuronal cultures, TAT-GluA2 3Y inhibits the internalization of GluA2‑containing AMPARs induced by NMDA or insulin. The peptide does not affect basal synaptic transmission or cell viability. In behavioral studies, the peptide has antinociceptive effects in rat models of neuropathic pain.
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| ln Vivo |
In vivo, TAT-GluA2 3Y (10‑100 ug/animal, administered by intrathecal (IT) injection) induces increased hind paw withdrawal latencies following thermal and mechanical stimuli in rats. It also exhibits antinociceptive effects in a rat model of neuropathic pain (chronic constriction injury, CCI). The peptide blocks LTD and reverses established hyperalgesia and allodynia. Additionally, TAT-GluA2 3Y (administered intraperitoneally or intracerebroventricularly) can alleviate pentobarbital‑induced spatial memory deficits and synaptic depression.
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| Enzyme Assay |
For cell‑free assays, the ability of TAT-GluA2 3Y to disrupt the interaction between the GluA2 subunit and its binding partners (e.g., GRIP1, PICK1) can be measured using an AlphaScreen or GST pull‑down assay. Recombinant GST‑GluA2 C‑terminus peptide (1 ug) is immobilized on glutathione‑Sepharose beads and incubated with HEK‑293 cell lysates overexpressing a binding partner (e.g., Myc‑GRIP1) in the presence of TAT-GluA2 3Y (0.1‑100 uM). After washing, bound proteins are eluted and detected by Western blotting. The IC50 for disruption is calculated. For direct binding, an SPR assay can be used.
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| Cell Assay |
For cellular assays, primary cortical or hippocampal neurons (DIV 12‑14) are cultured in 96‑well plates (50,000 cells/well). TAT-GluA2 3Y is added to the culture medium at concentrations of 1‑10 uM for 30‑60 min. For endocytosis assays, neurons are treated with NMDA (50 uM, 15 min) or DHPG (a group I mGluR agonist, 100 uM, 15 min) to induce AMPAR endocytosis. Surface and internalized AMPARs are quantified by biotinylation (surface proteins labeled with sulfo‑NHS‑biotin, 4degC; cells are then fixed and biotin is stripped; internalized biotinylated receptors are detected by streptavidin blot). TAT-GluA2 3Y blocks the decrease in surface GluA2 levels. For electrophysiology, brain slices (400 um) are prepared from rats. A stimulating electrode is placed in the Schaffer collateral pathway, and a recording electrode is placed in the CA1 stratum radiatum for fEPSP recording. Low‑frequency stimulation (LFS; 1 Hz, 900 pulses) is applied to induce LTD. TAT-GluA2 3Y (10 uM) is added to the perfusate 30 min before LFS. The peptide prevents the sustained depression of fEPSPs. For MTT viability assays, TAT-GluA2 3Y at 10 uM is not cytotoxic.
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| Animal Protocol |
In vivo studies are performed in male Sprague‑Dawley rats (250‑300 g). TAT-GluA2 3Y is dissolved in sterile saline (or 10% DMSO in saline) and administered by intrathecal (IT) injection (10‑100 ug in 20‑30 uL, lumbar puncture) or intracerebroventricular (ICV) injection (5‑20 ug in 5‑10 uL). For the chronic constriction injury (CCI) model of neuropathic pain, rats are anesthetized, and the left sciatic nerve is loosely ligated. After 7‑14 days, mechanical allodynia (paw withdrawal threshold, von Frey filaments) and thermal hyperalgesia (paw withdrawal latency, Hargreaves apparatus) are measured. TAT-GluA2 3Y is administered intrathecally, and thresholds are measured at 15, 30, 60, 120, and 240 min. The peptide reverses allodynia and hyperalgesia. For memory studies, mice are treated with pentobarbital (10 mg/kg IP) to induce spatial memory deficits. TAT-GluA2 3Y (20 ug ICV) is given 30 min before pentobarbital. The Morris water maze (hidden platform, 5 days) or the novel object recognition test is performed. The peptide rescues the memory deficit. For PK/PD, CSF and plasma are collected after ICV injection, and peptide concentrations are measured by ELISA or LC‑MS.
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| ADME/Pharmacokinetics |
As a peptide, TAT-GluA2 3Y (MW 2633.97, sequence: YGRKKRRQRRRYKEGYNVYG) is rapidly degraded in the blood (half‑life < 30 min). When administered ICV, the peptide distributes in the brain and CSF, with a half‑life of approximately 1‑2 hours in the CNS. It does not cross the BBB efficiently, so ICV or IT administration is required for CNS studies. The peptide is soluble in water (1 mg/mL) and in DMSO. Store as lyophilized powder at -20degC. For in vitro use, working solutions should be prepared in sterile water or PBS.
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| Toxicity/Toxicokinetics |
Preclinical toxicity data are limited. At intrathecal doses up to 100 ug in rats, no adverse effects on motor function (rotarod, open field) or body weight are observed. The peptide is not cytotoxic at 10 uM in primary neurons. Standard safety precautions for handling peptides should be followed. TAT-GluA2 3Y is for research use only.
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| References |
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| Additional Infomation |
TAT-GluA2 3Y (CAS 1404188-93-7) is a cell‑permeable interference peptide that blocks AMPAR endocytosis and long‑term depression (LTD). It is used as a research tool to study the role of AMPAR trafficking in synaptic plasticity, learning, memory, and neuropathic pain. The peptide has antinociceptive effects in animal models of chronic pain. It is not approved for clinical use. Storage: desiccated at -20degC.
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| Molecular Formula |
C115H185N43O29
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|---|---|
| Molecular Weight |
2633.97012114525
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| Exact Mass |
2633.435
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| CAS # |
1404188-93-7
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| PubChem CID |
146018956
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| Appearance |
White to off-white solid powder
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| LogP |
-14.2
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| Hydrogen Bond Donor Count |
49
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| Hydrogen Bond Acceptor Count |
39
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| Rotatable Bond Count |
98
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| Heavy Atom Count |
187
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| Complexity |
5720
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| Defined Atom Stereocenter Count |
17
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| SMILES |
O=C([C@H](CCCCN)NC([C@H](CCCCN)NC([C@H](CCCNC(=N)N)NC(CNC([C@H](CC1C=CC(=CC=1)O)N)=O)=O)=O)=O)N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(NCC(N[C@H](C(N[C@@H](CC(N)=O)C(N[C@H](C(N[C@H](C(NCC(=O)O)=O)CC1C=CC(=CC=1)O)=O)C(C)C)=O)=O)CC1C=CC(=CC=1)O)=O)=O)CCC(=O)O)=O)CCCCN)=O)CC1C=CC(=CC=1)O)=O)CCCNC(=N)N)=O)CCCNC(=N)N)=O)CCCNC(=N)N)=O)CCC(N)=O)=O)CCCNC(=N)N)=O)CCCNC(=N)N
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| InChi Key |
JRFBJZYZNDUYJM-NOEVYFGRSA-N
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| InChi Code |
InChI=1S/C115H185N43O29/c1-61(2)92(109(187)157-82(95(173)142-60-91(169)170)54-63-26-34-67(160)35-27-63)158-108(186)85(57-87(121)164)156-106(184)83(55-64-28-36-68(161)37-29-64)144-89(166)59-141-94(172)80(41-43-90(167)168)153-99(177)74(17-5-8-46-118)152-107(185)84(56-65-30-38-69(162)39-31-65)155-104(182)79(23-14-52-139-115(132)133)150-101(179)76(20-11-49-136-112(126)127)148-102(180)77(21-12-50-137-113(128)129)151-105(183)81(40-42-86(120)163)154-103(181)78(22-13-51-138-114(130)131)149-100(178)75(19-10-48-135-111(124)125)147-98(176)73(16-4-7-45-117)146-97(175)72(15-3-6-44-116)145-96(174)71(18-9-47-134-110(122)123)143-88(165)58-140-93(171)70(119)53-62-24-32-66(159)33-25-62/h24-39,61,70-85,92,159-162H,3-23,40-60,116-119H2,1-2H3,(H2,120,163)(H2,121,164)(H,140,171)(H,141,172)(H,142,173)(H,143,165)(H,144,166)(H,145,174)(H,146,175)(H,147,176)(H,148,180)(H,149,178)(H,150,179)(H,151,183)(H,152,185)(H,153,177)(H,154,181)(H,155,182)(H,156,184)(H,157,187)(H,158,186)(H,167,168)(H,169,170)(H4,122,123,134)(H4,124,125,135)(H4,126,127,136)(H4,128,129,137)(H4,130,131,138)(H4,132,133,139)/t70-,71-,72-,73-,74-,75-,76-,77-,78-,79-,80-,81-,82-,83-,84-,85-,92-/m0/s1
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| Chemical Name |
(4S)-4-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]acetyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]hexanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-oxopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]hexanoyl]amino]-5-[[2-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S)-1-(carboxymethylamino)-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-5-oxopentanoic 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) |
H2O: 100 mg/mL (37.97 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 100 mg/mL (37.97 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 | 0.3797 mL | 1.8983 mL | 3.7966 mL | |
| 5 mM | 0.0759 mL | 0.3797 mL | 0.7593 mL | |
| 10 mM | 0.0380 mL | 0.1898 mL | 0.3797 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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