title: Screening Anti-Cancer Drugs against Tubulin using Catch-and-Release Electrospray Ionization Mass Spectrometry.
abstract: Tubulin, which is the building block of microtubules, plays an important role in cell division. This critical role makes tubulin an attractive target for the development of chemotherapeutic drugs to treat cancer. Currently, there is no general binding assay for tubulin-drug interactions. The present work describes the application of the catch-and-release electrospray ionization mass spectrometry (CaR-ESI-MS) assay to investigate the binding of colchicinoid drugs to αβ-tubulin dimers extracted from porcine brain. Proof-of-concept experiments using positive (ligands with known affinities) and negative (non-binders) controls were performed to establish the reliability of the assay. The assay was then used to screen a library of seven colchicinoid analogues to test their binding to tubulin and to rank their affinities.
authors.affiliation: Department of Chemistry and Alberta Glycomics Center, University of Alberta, Edmonton, AB, T6G 2G2, Canada.
authors.forename: Reza
authors.initials: R
authors.lastname: Rezaei Darestani
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, AB, T6G 1Z2, Canada.
authors.forename: Philip
authors.initials: P
authors.lastname: Winter
authors.affiliation: Department of Chemistry and Alberta Glycomics Center, University of Alberta, Edmonton, AB, T6G 2G2, Canada.
authors.forename: Elena N
authors.initials: EN
authors.lastname: Kitova
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, AB, T6G 1Z2, Canada.
authors.forename: Jack A
authors.initials: JA
authors.lastname: Tuszynski
authors.affiliation: Department of Chemistry and Alberta Glycomics Center, University of Alberta, Edmonton, AB, T6G 2G2, Canada. john.klassen@ualberta.ca.
authors.forename: John S
authors.initials: JS
authors.lastname: Klassen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000032:analysis / Q000378:metabolism*; D001923:Brain Chemistry; D003078:Colchicine / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism; D055808:Drug Discovery / Q000379:methods*; D011485:Protein Binding; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013552:Swine; D014404:Tubulin / Q000378:metabolism*; D050257:Tubulin Modulators / Q000032:analysis / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D014404:Tubulin; D050257:Tubulin Modulators; D003078:Colchicine
keywords: Affinity; Binding; Drug; Tubulin