| 包装 | 价格(元) |
| 500 ?g | 电议 |
| 1mg | 电议 |
Didemnin B is a cyclic depsipeptide produced by marine tunicates that specifically binds the GTP-bound conformation of EEF1A.
Preparation Method |
The eEF1A·GTP·Mg2+ and Didemnin B·eEF1A·GTP·Mg2+ complexes were solvated by adding a spherical shell of ~3000 TIP3P water molecules centered at CG1 of Leu77. The radius of this water shell was 35 A to ensure the solvation of the interdomain cleft in both complexes. These water molecules were first energy-minimized, and then both waters and all protein residues were allowed to relax. In each case, 1000 steps of steepest descent were followed by 2000 steps of conjugate gradient energy minimization. The final coordinate sets were used as input for the subsequent MD simulations. SHAKE was used for all bonds, and the integration time step was 2 fs. Only the water molecules were free to move for the first 100 ps. For the remaining 2000 ps the whole system was allowed to relax. |
Applications |
Didemnin B specifically binds GTP-bound eEF1A-1, in a location between the aa-tRNA-binding and GTP-binding domains, but distinct from the actin-binding domain. Didemnin B thereby specifically inhibits eEF1A-1 release from the ribosomal A-site, preventing peptidyl-tRNA translocation and subsequent peptide elongation. |
Cell lines |
HepG2 cells |
Preparation Method |
Cells were treated with palmitate, with or without 80 nM didemnin B, followed by assessment of ER stress (6 h), protein synthesis (6-24 h), and cell death (48 h). |
Reaction Conditions |
80 nM didemnin B for 6-48 h |
Applications |
Didemnin B prevent upregulation of GRP78 protein in HepG2 cells，in association with sustained inhibition of protein synthesis. |
Animal models |
Five-week-old male C57BL/6J and leptin-deficient (ob/ob) mice on a C57BL/6J background |
Preparation Method |
Used 5-week-old male C57BL/6J (lean control) and leptin-deficient ob/ob mice. All mice were fed AIN-76A diet for 4 weeks. During week 5, mice were given i.p. injections of didemnin B (50 μg/kg) or vehicle control on days 1, 4, and 7. |
Dosage form |
didemnin B (50 μg/kg) on days 1, 4, and 7( i.p. injections) |
Applications |
Didemnin B treatment modestly reduces food consumption in obese mice. |
| 半岛bd体育手机客户端 描述 | Didemnin B is a cyclic depsipeptide produced by marine tunicates that specifically binds the GTP-bound conformation of EEF1A, inhibiting its release from the ribosomal A site and preventing subsequent peptide elongation.Didemnin B thereby specifically inhibits eEF1A-1 release from the ribosomal A-site, preventing peptidyl-tRNA translocation and subsequent peptide elongation. It is a potential anticancer, antiviral, and immunosuppressive agent[1,2]. Didemnin B (80 nM,48h) prevent upregulation of GRP78 protein in HepG2 cells,in association with sustained inhibition of protein synthesis[3]. The structurally unrelated cyclic peptides didemnin B and ternatin-4 bind to the eEF1A(GTP)-aa-tRNA ternary complex and inhibit translation but have different effects on protein synthesis in vitro and in vivo. By binding to a common site on eEF1A, didemnin B and ternatin-4 trap eEF1A in an intermediate state of aa-tRNA selection, preventing eEF1A release and aa-tRNA accommodation on the ribosome[5]. Didemnin B can induce apoptosis in a wide range of transformed cell lines[6]. Acute intervention with the EEF1A inhibitor, didemnin B, improves hepatic lipotoxicity in obese mice with NAFLD through mechanisms not entirely dependent on decreased food intake, suggesting a potential therapeutic strategy for this ER stress-related disease[4].Didemnin B improves hepatic steatosis, glucose tolerance, and blood lipids in obesity, in association with moderate, possibly hormetic, upregulation of pathways involved in cell stress response and energy balance in the liver[7]. References: |
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