Ganesh Thota, Brodie Peggy J, Banerjee Abhijit, Bane Susan, Kingston David G I
Department of Chemistry and Virginia Tech Center for Drug Discovery, M/C 0212, Virginia Tech, Blacksburg, VA, 24061, USA.
J Labelled Comp Radiopharm. 2014 Feb;57(2):78-81. doi: 10.1002/jlcr.3144. Epub 2013 Dec 5.
The epothilones, including epothilones B and D, are macrocyclic lactones, which have potent cytotoxicities and promote the polymerization of tubulin to mictotubules by binding to and stabilizing the tubulin polymer. They have a very similar mechanism of action to paclitaxel (Taxol®). The determination of the microtubule-binding conformation of the epothilones is an important piece of information in designing improved analogs for possible clinical use, and internuclear distance information that will assist the determination of this conformation can be obtained by rotational echo double resonance (REDOR) NMR studies of microtubule-bound epothilones with appropriate stable isotope labels. Analogs of epothilone B and epothilone D with [(2) H3 ] and [(19) F] labels were prepared from an advanced precursor for potential use in REDOR NMR studies to determine internuclear distances in tubulin-bound ligand.
埃坡霉素，包括埃坡霉素B和D，是大环内酯类化合物，具有强大的细胞毒性，通过与微管蛋白聚合物结合并使其稳定，促进微管蛋白聚合成微管。它们的作用机制与紫杉醇（泰素®）非常相似。确定埃坡霉素的微管结合构象是设计可能用于临床的改良类似物的重要信息，通过对结合有适当稳定同位素标记的微管的埃坡霉素进行旋转回波双共振（REDOR）核磁共振研究，可以获得有助于确定这种构象的核间距离信息。用[(2)H3]和[(19)F]标记的埃坡霉素B和埃坡霉素D的类似物由一种高级前体制备而成，用于REDOR核磁共振研究，以确定与微管蛋白结合的配体中的核间距离。
