Design, synthesis and biological evaluation of a simplified fluorescently labeled discodermolide as a molecular probe to study the binding of discodermolide to tubulin

  • Bioorg Med Chem. 2011 Sep 1;19(17):5247-54. doi: 10.1016/j.bmc.2011.06.082.
Jun Qi  1 ,  Adam R Blanden ,  Susan Bane ,  David G I Kingston
Affiliations
  • 1. Department of Chemistry, Virginia Tech, Blacksburg, VA 24061, USA.
PMID: 21802957 DOI: 10.1016/j.bmc.2011.06.082
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.