title: Design, synthesis and biological evaluation of a simplified fluorescently labeled discodermolide as a molecular probe to study the binding of discodermolide to tubulin.
abstract: The design, synthesis, and biological evaluation of a simplified fluorescently labeled discodermolide analogue possessing a dimethylaminobenzoyl fluorophore has been achieved. Stereoselective Suzuki coupling and Horner-Wadsworth-Emmons reaction comprised the key tactics for its construction. The analogue exhibited qualitatively similar activity to paclitaxel in a tubulin assembly assay, and it can thus be used as a fluorescent molecular probe to explore the local environment of the discodermolide binding site on tubulin. The results of fluorescence measurements on the tubulin-bound analogue are reported.
authors.affiliation: Department of Chemistry, Virginia Tech, Blacksburg, VA 24061, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Qi
authors.forename: Adam R
authors.initials: AR
authors.lastname: Blanden
authors.forename: Susan
authors.initials: S
authors.lastname: Bane
authors.forename: David G I
authors.initials: DG
authors.lastname: Kingston
mesh_terms: D000473:Alkanes / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D002219:Carbamates / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D045744:Cell Line, Tumor; D015195:Drug Design; D005456:Fluorescent Dyes / Q000737:chemistry*; D006801:Humans; D007783:Lactones / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D017239:Paclitaxel / Q000737:chemistry / Q000633:toxicity; D011485:Protein Binding; D011753:Pyrones / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D014404:Tubulin / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000473:Alkanes; D000970:Antineoplastic Agents; D002219:Carbamates; D005456:Fluorescent Dyes; D007783:Lactones; D011753:Pyrones; D014404:Tubulin; C071229:discodermolide; D017239:Paclitaxel