Analysis of purified tubulin in high concentration of glutamate for application in high throughput screening for microtubule-stabilizing agents

Assay Drug Dev Technol. 2004 Dec;2(6):621-8. doi: 10.1089/adt.2004.2.621.

Abstract

High-throughput screening (HTS) is a powerful approach for the discovery of potential and effective drugs from a number of candidates. The dynamics of tubulin assembly and disassembly in vitro are an important target for the screening of anti-tumor agents. However, previously described methods are not amenable for HTS. In this paper, we compared preparation methods of tubulin and suggest a combination method, i.e., one cycle of assembly and disassembly following ion-exchange chromatography using high concentrations of glutamate to increase the recovery of tubulin with high purity. The resultant highly purified microtubule-associated proteins-free tubulin in high glutamate solution was directly employed in tubulin polymerization assays. Our results indicate that the system is feasible and practicable as a model for HTS for microtubule-stabilizing agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatography, DEAE-Cellulose
  • Combinatorial Chemistry Techniques
  • Drug Evaluation, Preclinical
  • Glutamic Acid / chemistry*
  • Guanosine Triphosphate / chemistry
  • Microscopy, Electron
  • Microtubules / drug effects*
  • Polymers / chemical synthesis
  • Tubulin / chemistry*
  • Tubulin / isolation & purification

Substances

  • Polymers
  • Tubulin
  • Glutamic Acid
  • Guanosine Triphosphate