Leptomycin B Chemische Eigenschaften,Einsatz,Produktion Methoden
R-Sätze Betriebsanweisung:
R23/25:Giftig beim Einatmen und Verschlucken.
R36/38:Reizt die Augen und die Haut.
S-Sätze Betriebsanweisung:
S7:Behälter dicht geschlossen halten.
S16:Von Zündquellen fernhalten - Nicht rauchen.
S24:Berührung mit der Haut vermeiden.
S33:Maßnahmen gegen elektrostatische Aufladungen treffen.
S45:Bei Unfall oder Unwohlsein sofort Arzt zuziehen (wenn möglich, dieses Etikett vorzeigen).
Verwenden
Leptomycin B is the dominant and most studied member of the leptomycin class, isolated from selected Streptomyces strains. Leptomycin B is a nanomolar active and specific nuclear export inhibitor. Its target is CRM1/exportin1, a protein in the nuclear export sequence (NES). Proteins affected include c-Abl, cyclin B1, HIV-1 Rev, IκB, MPF, MAP/ERK, MDM2/p53, NF-κB/IκB7 and PKA. Leptomycin B inhibits export of many RNAs, e.g. COX-2 and c-FOS mRNA. Leptomycin B also shows antifungal and antibacterial and potent antitumour activities.
Definition
ChEBI: A leptomycin having a (2E,10E,12E,16Z,18E)-double bond configuration as well as an ethyl substituent at position 17.
Allgemeine Beschreibung
Leptomycin B is an anti-fungal antibiotic, anti-tumor cytotoxin that inhibits CRM1-dependent, NES-dependent nucleo-cytoplasmic translocation (nuclear export inhibitor). NES containing proteins include HIV-1 REV; actin, c-Abl, cyclin B1, MDM2/p53, I?B, MPF, PKA and MEK.
Biologische Aktivität
Antifungal antibiotic that is an inhibitor of the nuclear export of proteins; acts by binding directly to and inhibiting CRM1/exportin-1. Inhibits the nuclear export of the HIV regulatory protein Rev and stabilizes p53. Antitumor in vitro and in vivo .
Mechanism of action
The nuclear export inhibition mechanism involves the direct binding of Leptomycin B to exportin1, which blocks the binding of exportin1 to proteins containing the leucine-rich NES. Later, NES-exportin1 interaction was identified on a conserved region near cysteine-529 residue of human exportin1. This cysteine-529 residue on exportin1 provides LMB sensitivity because unsaturated γ-lactone in LMB undergoes a Michael-type reaction by the sulfhydryl group on cysteine residue. Once LMB is bound to exportin1, the NES-bearing nuclear export cargo fails to bind the receptor.
Leptomycin B Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
