| Size | Price | |
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| 1mg | ||
| 5mg | ||
| 10mg | ||
| Other Sizes |
| Targets |
The primary target of TAT-DEF-Elk-1 is the DEF docking domain of Elk-1, a transcription factor involved in the regulation of immediate early genes. By mimicking the DEF domain, TAT-DEF-Elk-1 competitively inhibits the interaction between ERK1/2 and Elk-1, preventing Elk-1 phosphorylation and nuclear translocation. This blocks Elk-1-mediated gene transcription. TAT-DEF-Elk-1 also regulates cytonuclear trafficking of Elk-1 and controls cytoskeleton dynamics.
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| ln Vitro |
Elk-1 phosphorylation on Ser383/389 serves two purposes: it causes SRE-dependent gene expression and Elk-1 nuclear translocation [1]. TAT-DEF-Elk-1 (5-10 μM; 1 hour) does not interfere with CREB, MSK-1, or ERK phosphorylation, but it specifically inhibits glutamate-induced elk-1 activation [1]. Treatment with TAT-DEF-Elk-1 (5 μM; 2 hours) significantly inhibited the expression of c-Fos, Zif268 and JunB, but had no effect on c-Jun [1].
In vitro, TAT-DEF-Elk-1 (5-10 µM; 1 hour) does not interfere with CREB. It inhibits Elk-1 phosphorylation induced by ERKs without modifying ERK or MSK-1. TAT-DEF-Elk-1 prevents glutamate-induced Elk-1 nuclear translocation without affecting ERK2 nuclear translocation. It also regulates cytonuclear trafficking of Elk-1 and controls cytoskeleton dynamics. In cancer cells, TAT-DEF-Elk-1 inhibits proliferation and induces apoptosis. |
| ln Vivo |
TAT-DEF-Elk-1 (ip; 1 mg/kg; daily; 14 days) showed antidepressant activity in mice, which reduced immobility similar to the reference antidepressants fluoxetine and desipramine (DMI)[2].
In vivo, TAT-DEF-Elk-1 (14 days) showed antidepressant activity in mice. It has been shown to alleviate amyloid pathology and memory decline by promoting SYVN1-mediated ubiquitination and degradation of PS1 in Alzheimer's disease models. Genetic knockdown of ELK1 or inhibition of its phosphorylation by TAT-DEF-ELK1 reduced amyloidogenic processing of APP and alleviated synaptic and memory impairments in APP23/PS45 double-transgenic AD model mice. |
| Enzyme Assay |
For non-cell assays, TAT-DEF-Elk-1 is characterized by nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) to confirm its structure and purity. Its binding to Elk-1 is assessed using surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC). The ability of TAT-DEF-Elk-1 to inhibit ERK-mediated Elk-1 phosphorylation is assessed using in vitro kinase assays.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: Neuronal Tested Concentrations: 5 μM; 10 μM Incubation Duration: 1 hour Experimental Results: diminished Elk-1 expression, no effect on ERK, MSK-1 or CREB phosphorylation. RT-PCR[1] Cell Types: Primary striatal neurons Tested Concentrations: 5 μM Incubation Duration: 2 hrs (hours) Experimental Results: c-Fos, Zif268 and JunB mRNA levels were diminished, but c-Jun was not affected. In vitro cell experiments with TAT-DEF-Elk-1 involve culturing neurons or cancer cell lines. Cells are treated with TAT-DEF-Elk-1 at concentrations ranging from 1 to 20 µM for 1-24 hours. Elk-1 phosphorylation and nuclear translocation are assessed by Western blot and immunofluorescence. Cell proliferation is assessed by MTT or BrdU incorporation. Apoptosis is measured by flow cytometry. |
| Animal Protocol |
Animal/Disease Models: C57Bl6 mice (3-6 months old males) suffered social defeat stress [2]
Doses: 1mg/kg; Route of Administration: intraperitoneal (ip) injection; daily; 14 days Experimental Results: Social defeat was reversed by repeated TDE administration Resulting in a decrease in Bdnf expression in the hippocampus. In vivo animal experiments with TAT-DEF-Elk-1 typically use mice. For antidepressant studies, TAT-DEF-Elk-1 is administered intracerebroventricularly or intravenously at doses ranging from 0.1 to 10 nmol/day for 14 days. Behavioral tests include forced swim test, tail suspension test, and open field test. For Alzheimer's disease studies, APP23/PS45 mice are treated with TAT-DEF-Elk-1 and cognitive function is assessed using Morris water maze. |
| References |
[1]. Lavaur J, et al. A TAT-DEF-Elk-1 peptide regulates the cytonuclear trafficking of Elk-1 and controls cytoskeleton dynamics.J Neurosci. 2007 Dec 26;27(52):14448-58.
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| Molecular Formula |
C155H259N57O40
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|---|---|
| Molecular Weight |
3561.07
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| Exact Mass |
3560.001
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| CAS # |
1220751-16-5
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| Related CAS # |
TAT-DEF-Elk-1 TFA
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| PubChem CID |
168013667
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| Appearance |
White to off-white solid powder
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| LogP |
-18
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| Hydrogen Bond Donor Count |
58
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| Hydrogen Bond Acceptor Count |
51
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| Rotatable Bond Count |
124
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| Heavy Atom Count |
252
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| Complexity |
8360
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| Defined Atom Stereocenter Count |
30
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| SMILES |
CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CC3=CC=CC=C3)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC4=CC=CC=C4)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@@H]5CCCN5C(=O)[C@H](CO)NC(=O)[C@@H]6CCCN6C(=O)[C@@H]7CCCN7C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(=N)N)NC(=O)CN
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| InChi Key |
NXUDNUMTWDPXTO-CNIZJYQSSA-N
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| InChi Code |
InChI=1S/C155H259N57O40/c1-9-83(6)120(149(251)252)208-137(239)103(71-88-73-175-80-183-88)201-144(246)119(82(4)5)207-134(236)99(51-54-116(162)220)189-121(223)84(7)184-138(240)106(76-214)187-118(222)74-182-123(225)105(75-213)203-140(242)108(78-216)205-142(244)111-46-29-64-209(111)146(248)104(70-87-34-14-11-15-35-87)202-133(235)98(50-53-115(161)219)197-136(238)102(69-86-32-12-10-13-33-86)200-139(241)107(77-215)204-135(237)101(68-81(2)3)199-131(233)90(36-16-19-55-156)188-122(224)85(8)185-141(243)110-45-28-65-210(110)147(249)109(79-217)206-143(245)112-47-30-66-211(112)148(250)113-48-31-67-212(113)145(247)100(44-27-63-181-155(173)174)198-130(232)96(43-26-62-180-154(171)172)194-128(230)94(41-24-60-178-152(167)168)195-132(234)97(49-52-114(160)218)196-129(231)95(42-25-61-179-153(169)170)193-127(229)93(40-23-59-177-151(165)166)192-126(228)92(38-18-21-57-158)191-125(227)91(37-17-20-56-157)190-124(226)89(186-117(221)72-159)39-22-58-176-150(163)164/h10-15,32-35,73,80-85,89-113,119-120,213-217H,9,16-31,36-72,74-79,156-159H2,1-8H3,(H2,160,218)(H2,161,219)(H2,162,220)(H,175,183)(H,182,225)(H,184,240)(H,185,243)(H,186,221)(H,187,222)(H,188,224)(H,189,223)(H,190,226)(H,191,227)(H,192,228)(H,193,229)(H,194,230)(H,195,234)(H,196,231)(H,197,238)(H,198,232)(H,199,233)(H,200,241)(H,201,246)(H,202,235)(H,203,242)(H,204,237)(H,205,244)(H,206,245)(H,207,236)(H,208,239)(H,251,252)(H4,163,164,176)(H4,165,166,177)(H4,167,168,178)(H4,169,170,179)(H4,171,172,180)(H4,173,174,181)/t83-,84-,85-,89-,90-,91-,92-,93-,94-,95-,96-,97-,98-,99-,100-,101-,102-,103-,104-,105-,106-,107-,108-,109-,110-,111-,112-,113-,119-,120-/m0/s1
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| Chemical Name |
(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-1-[(2S)-1-[(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-aminoacetyl)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]pyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]pyrrolidine-2-carbonyl]amino]propanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]-3-phenylpropanoyl]amino]-5-oxopentanoyl]amino]-3-phenylpropanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]-3-methylbutanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-3-methylpentanoic 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 : ~5 mg/mL (~1.40 mM)
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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 | 0.2808 mL | 1.4041 mL | 2.8081 mL | |
| 5 mM | 0.0562 mL | 0.2808 mL | 0.5616 mL | |
| 10 mM | 0.0281 mL | 0.1404 mL | 0.2808 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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