Chemistry:Leptomycin
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| Preferred IUPAC name
(2E,5S,6R,7S,9R,10E,12E,15R,16Z,18E)-17-Ethyl-6-hydroxy-3,5,7,9,11,15-hexamethyl-19-[(2S,3S)-3-methyl-6-oxo-3,6-dihydro-2H-pyran-2-yl]-8-oxononadeca-2,10,12,16,18-pentaenoic acid | |
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3D model (JSmol)
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| Properties | |
| C33H48O6 | |
| Molar mass | 540.741 g·mol−1 |
| Density | 1.072 g/mL |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). | |
 verify (what is   ?)
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Leptomycins are secondary metabolites produced by Streptomyces spp.
Leptomycin B (LMB) was originally discovered as a potent antifungal compound. [1] Leptomycin B was found to cause cell elongation of the fission yeast Schizosaccharomyces pombe. Since then this elongation effect has been used for the bioassay of leptomycin. However, recent data shows that leptomycin causes G1 cell cycle arrest in mammalian cells and is a potent anti-tumor agent against murine experimental tumors in combination therapy.[2]
Leptomycin B has been shown to be a potent and specific nuclear export inhibitor in humans[3] and the fission yeast S. pombe.[4] Leptomycin B alkylates and inhibits CRM1 (chromosomal region maintenance)/exportin 1 (XPO1), a protein required for nuclear export of proteins containing a nuclear export sequence (NES), by glycosylating a cysteine residue (cysteine 529 in S. pombe).[5] In addition to antifungal and antibacterial activities, leptomycin B blocks the cell cycle and is a potent anti-tumor agent. At low nM concentrations, leptomycin B blocks the nuclear export of many proteins including HIV-1 Rev, MAPK/ERK, and NF-κB/IκB, and it inhibits the inactivation of p53.[6] Leptomycin B also inhibits the export and translation of many RNAs, including COX-2 and c-Fos mRNAs, by inhibiting the export of ribonucleoproteins.[citation needed]
Leptomycin A (LPA) was discovered together with LMB. LMB is twice as potent as LPA.[clarification needed]
See also
- Selective inhibitor of nuclear export
References
- ↑ "Leptomycins A and B, new antifungal antibiotics. II. Structure elucidation". J. Antibiot. 36 (6): 646–50. 1983. doi:10.7164/antibiotics.36.646. PMID 6874586.
- ↑ Lu, Chuanwen; Changxia Shao; Everardo Cobos; Kamaleshwar P. Singh; Weimin Gao (March 2012). "Chemotherapeutic Sensitization of Leptomycin B Resistant Lung Cancer Cells by Pretreatment with Doxorubicin". PLOS ONE (United States) 7 (3): e32895. doi:10.1371/journal.pone.0032895. ISSN 1932-6203. PMID 22412944. Bibcode: 2012PLoSO...732895L.
- ↑ "Leptomycin B inhibition of signal-mediated nuclear export by direct binding to CRM1". Exp. Cell Res. 242 (2): 540–7. August 1998. doi:10.1006/excr.1998.4136. PMID 9683540.
- ↑ "Leptomycin B targets a regulatory cascade of crm1, a fission yeast nuclear protein, involved in control of higher order chromosome structure and gene expression". J. Biol. Chem. 269 (9): 6320–4. March 1994. doi:10.1016/S0021-9258(17)37374-X. PMID 8119981. http://www.jbc.org/content/269/9/6320.abstract.
- ↑ "Leptomycin B inactivates CRM1/exportin 1 by covalent modification at a cysteine residue in the central conserved region". Proc. Natl. Acad. Sci. U.S.A. 96 (16): 9112–7. August 1999. doi:10.1073/pnas.96.16.9112. PMID 10430904. Bibcode: 1999PNAS...96.9112K.
- ↑ "Activation of p53 in cervical carcinoma cells by small molecules.". Proc Natl Acad Sci U S A 97 (15): 8501–6. 2000. doi:10.1073/pnas.97.15.8501. PMID 10900010. Bibcode: 2000PNAS...97.8501H.
External links
- leptomycin+B at the US National Library of Medicine Medical Subject Headings (MeSH)
Original data copied with permission from Leptomycin B manufacturer product page (Fermentek)
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