Asset Details

MbrlCatalogueTitleDetail

Do you wish to reserve the book?

A fluorescence anisotropy assay to discover and characterize ligands targeting the maytansine site of tubulin

by Prota, Andrea E. , Jansen, Rolf , Paterson, Ian , Müller, Rolf , Menchon, Grégory , Steinmetz, Michel O. , Irschik, Herbert , Díaz, J. Fernando , Lucena-Agell, Daniel , Altmann, Karl-Heinz , Bucher, Pascal

in 631/1647/1888 / 631/45/612 / 631/535/1266 / 631/92/613 / Ado-Trastuzumab Emtansine / Animals / Anisotropy / Antineoplastic Agents - metabolism / Assaying / Binding Sites / Cancer / Crystal structure / Fluorescence / Fluorescence Polarization - methods / Humanities and Social Sciences / Humans / Ligands / Macrolides - metabolism / Maytansine - analogs & derivatives / Maytansine - metabolism / Microtubules - metabolism / Molecular chains / Monoclonal antibodies / multidisciplinary / Natural products / Oxazoles - metabolism / Paclitaxel / Pharmacology / Science / Science (multidisciplinary) / Targeted cancer therapy / Taxol / Trastuzumab / Trastuzumab - metabolism / Tubulin / Tubulin - metabolism / Vinblastine

2018

Yes Please

Hey, we have placed the reservation for you!

By the way, why not check out events that you can attend while you pick your title.

Oops! Something went wrong.

Looks like we were not able to place the reservation. Kindly try again later.

Are you sure you want to remove the book from the shelf?

A fluorescence anisotropy assay to discover and characterize ligands targeting the maytansine site of tubulin

2018

Confirm

Do you wish to request the book?

A fluorescence anisotropy assay to discover and characterize ligands targeting the maytansine site of tubulin

2018

Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy

How would you like to get it?

Submit

We have requested the book for you!

Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.

Oops! Something went wrong.

Looks like we were not able to place your request. Kindly try again later.

Journal Article

A fluorescence anisotropy assay to discover and characterize ligands targeting the maytansine site of tubulin

Prota, Andrea E.,

Jansen, Rolf,

Paterson, Ian,

Müller, Rolf,

Menchon, Grégory,

Steinmetz, Michel O.,

Irschik, Herbert,

Díaz, J. Fernando,

Lucena-Agell, Daniel,

Altmann, Karl-Heinz,

Bucher, Pascal

2018

Overview

Microtubule-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. Microtubule-targeting agents are used successfully as anticancer therapeutics. Here authors develop a fluorescence-anisotropy-based assay to identify and characterize ligands for the maytansine site of tubulin and provide crystal structures of identified ligands in complex with tubulin.

Share this book

Add to My Shelf

Publisher

Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio

Subject

/ Ado-Trastuzumab Emtansine

/ Animals

/ Anisotropy