Tubulin-binding drug screening by MALDI-TOFMS.
Despite a large amount of drugs available to treat cancer, none is totally satisfactory with respect to its tolerance or side effects. It is very important to discover new compounds that exhibit specific features such as binding to proteic targets. Given the clinical successes of the poisons of the mitotic spindle chemotherapeutic agent class, it is often considered that tubulin represents one of the best cancer targets identified so far, and it seems likely that discovering new drugs of this class will significantly improve the range of active chemotherapeutic agents. The aim of this work is to present the new screening test that has been developed in our laboratory in order to study the binding of compounds to tubulin. We have developed a screening protocol involving three sampling strategies before the MALDI-TOFMS analysis. The three strategies give very accurate and reproducible results and could therefore possibly be used in screening campaigns. We have also proved that no unspecific binding can provide a loss of specificity of the test. Our protocol presents all the requirements for being a useful tool to screen the binding of compounds to tubulin.
Hannewald
Paul
P
Laboratoire de Spectrométrie de Masse et de Chimie Laser, 1, Boulevard Arago, F-57078 METZ Technopôle 2000 Cedex 03, France.
Maunit
Benoît
B
Muller
Jean-François
JF
D004364:Pharmaceutical Preparations / Q000378:metabolism*; D015203:Reproducibility of Results; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D014404:Tubulin / Q000378:metabolism*
D004364:Pharmaceutical Preparations; D014404:Tubulin