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|BBF-04477||1 mg||$1099||In stock|
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Didemnin B is a cyclic depsipeptide isolated from the extract of Trididemnum solidum. It exhibits antiviral and antineoplastic effects.
|Synonyms||N-(L-Lac-L-Pro-N-Methyl-D-Leu-)cyclo[L-Thr*-[(3S,4R)-3-hydroxy-4-[(S)-1-methylpropyl]-γAbu-]-[(2S,4S)-4-hydroxy*-2,5-dimethyl-3-oxohexanoyl]-L-Leu-L-Pro-N,O-dimethyl-L-Tyr-]; NSC-325319; Didemnin A, N-(1-(2-hydroxy-1-oxopropyl)-L-prolyl)-, (S)-|
|Storage||Store at -20°C|
|Antibiotic Activity Spectrum||Neoplastics (Tumor); Viruses|
|Boiling Point||1274.4°C at 760 mmHg|
|Solubility||Soluble in Methanol|
1. Mechanism of protein synthesis inhibition by didemnin B in vitro
B V SirDeshpande, P L Toogood Biochemistry . 1995 Jul 18;34(28):9177-84. doi: 10.1021/bi00028a030.
The cytotoxic and immunosuppressive marine depsipeptide didemnin B is a potent inhibitor of protein biosynthesis in intact cells. Here, didemnin B is shown to inhibit protein synthesis in vitro during the elongation cycle, by preventing eukaryotic elongation factor 2-(eEF-2-) dependent translocation. No inhibition of aminoacyl-tRNA delivery or of peptidyltransferase activity is observed. Didemnin B stimulates eEF-1 alpha-dependent aminoacyl-tRNA binding to rabbit reticulocyte ribosomes, and eEF-1 alpha is required for inhibition of the subsequent translocation of phenylalanyl-tRNA(Phe) from the A- to the P-site. These observations suggest that didemnin B prevents translocation by stabilizing aminoacyl-tRNA bound to the ribosomal A-site, similar to the antibiotic kirromycin, and consistent with the known affinity of didemnins for elongation factor eEF-1 alpha [Crews et al. (1994) J. Biol. Chem. 269, 15411]. Unlike kirromycin, didemnin B does not prevent peptide bond formation, so inhibition is observed only at the translocation step. Inhibition of translocation by didemnin B is attenuated by increasing concentrations of eEF-2.
2. Didemnin B and ternatin-4 differentially inhibit conformational changes in eEF1A required for aminoacyl-tRNA accommodation into mammalian ribosomes
Manuel F Juette, Sichen Shao, Jack Taunton, Alan Brown, Jordan D Carelli, Michael R Wasserman, Scott C Blanchard, Emily J Rundlet, Angelica Ferguson, Mikael Holm Elife . 2022 Oct 20;11:e81608. doi: 10.7554/eLife.81608.
Rapid and accurate mRNA translation requires efficient codon-dependent delivery of the correct aminoacyl-tRNA (aa-tRNA) to the ribosomal A site. In mammals, this fidelity-determining reaction is facilitated by the GTPase elongation factor-1 alpha (eEF1A), which escorts aa-tRNA as an eEF1A(GTP)-aa-tRNA ternary complex into the ribosome. 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. Here, we employ single-molecule fluorescence imaging and cryogenic electron microscopy to determine how these natural products inhibit translational elongation on mammalian ribosomes. 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. We also show that didemnin B and ternatin-4 exhibit distinct effects on the dynamics of aa-tRNA selection that inform on observed disparities in their inhibition efficacies and physiological impacts. These integrated findings underscore the value of dynamics measurements in assessing the mechanism of small-molecule inhibition and highlight potential of single-molecule methods to reveal how distinct natural products differentially impact the human translation mechanism.
3. Didemnin B induces apoptosis in proliferating but not resting peripheral blood mononuclear cells
D R Grubb, M A Baker, A Lawen Apoptosis . 2002 Oct;7(5):407-12. doi: 10.1023/a:1020078907108.
We have previously shown that didemnin B, a branched cyclic depsipeptide composed of seven amino acids and two hydroxy acids, can induce rapid and complete apoptosis in HL-60 cells (Grubb, D.R. et al. (1995) Biochem. Biophys. Res. Commun. 215, 1130-1136). We now report that didemnin B can induce apoptosis in a wide range of transformed cell lines. Resting normal lymphocytes, however, are apparently unaffected by exposure to the drug. To investigate whether cell transformation, and/or cell proliferation is necessary for didemnin B to induce apoptosis, we examined the effect of didemnin B on freshly harvested human lymphocytes before and after stimulation with concanavalin A. Didemnin B induced apoptosis in normal lymphocytes only after mitogenic stimulation and therefore warrants further examination for its potential as a chemotherapeutic agent, especially for treatment of leukemia.
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
* Total Molecular Weight:
Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
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