A fluorescence anisotropy assay to discover and characterize ligands targeting the maytansine site of tubulin.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Prota, Andrea E
Díaz, J Fernando
Steinmetz, Michel O
MetadataShow full item record
AbstractMicrotubule-targeting agents (MTAs) like taxol and vinblastine are among the most successful chemotherapeutic drugs against cancer. Here, we describe a fluorescence anisotropy-based assay that specifically probes for ligands targeting the recently discovered maytansine site of tubulin. Using this assay, we have determined the dissociation constants of known maytansine site ligands, including the pharmacologically active degradation product of the clinical antibody-drug conjugate trastuzumab emtansine. In addition, we discovered that the two natural products spongistatin-1 and disorazole Z with established cellular potency bind to the maytansine site on β-tubulin. The high-resolution crystal structures of spongistatin-1 and disorazole Z in complex with tubulin allowed the definition of an additional sub-site adjacent to the pocket shared by all maytansine-site ligands, which could be exploitable as a distinct, separate target site for small molecules. Our study provides a basis for the discovery and development of next-generation MTAs for the treatment of cancer.
AffiliationHelmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.
The following license files are associated with this item:
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 3.0 United States
- A new tubulin-binding site and pharmacophore for microtubule-destabilizing anticancer drugs.
- Authors: Prota AE, Bargsten K, Diaz JF, Marsh M, Cuevas C, Liniger M, Neuhaus C, Andreu JM, Altmann KH, Steinmetz MO
- Issue date: 2014 Sep 23
- Rhizoxin binding to tubulin at the maytansine-binding site.
- Authors: Takahashi M, Iwasaki S, Kobayashi H, Okuda S, Murai T, Sato Y
- Issue date: 1987 Dec 7
- Maytansine inhibits nucleotide binding at the exchangeable site of tubulin.
- Authors: Huang AB, Lin CM, Hamel E
- Issue date: 1985 May 16
- Effects of Tau and MAP2 on the interaction of maytansine with tubulin: inhibitory effect of maytansine on vinblastine-induced aggregation of tubulin.
- Authors: Fellous A, Ludueña RF, Prasad V, Jordan MA, Anderson W, Ohayon R, Smith PT
- Issue date: 1985 Oct
- Binding of maytansine to tubulin: competition with other mitotic inhibitors.
- Authors: Lin CM, Hamel E, Wolpert-DeFilippes MK
- Issue date: 1981 Mar