| Autor: |
Pérez-Peña H; Department of Chemistry, Università degli Studi di Milano, Via Golgi 19, 20133 Milan, Italy.; Laboratory of Chemoinformatics, Faculty of Chemistry, University of Strasbourg, 4, Rue Blaise Pascal, 67081 Strasbourg, France., Abel AC; Department of Chemistry, Università degli Studi di Milano, Via Golgi 19, 20133 Milan, Italy.; Laboratory of Biomolecular Research, Paul Scherrer Institute, Forschungsstrasse 111, 5232 Villigen, Switzerland., Shevelev M; Laboratory of Chemoinformatics, Faculty of Chemistry, University of Strasbourg, 4, Rue Blaise Pascal, 67081 Strasbourg, France.; Department of Biochemistry and Molecular Biology, Universitat de Barcelona, Gran Via de les Corts Catalanes, 585, 08007 Barcelona, Spain., Prota AE; Laboratory of Biomolecular Research, Paul Scherrer Institute, Forschungsstrasse 111, 5232 Villigen, Switzerland., Pieraccini S; Department of Chemistry, Università degli Studi di Milano, Via Golgi 19, 20133 Milan, Italy., Horvath D; Laboratory of Chemoinformatics, Faculty of Chemistry, University of Strasbourg, 4, Rue Blaise Pascal, 67081 Strasbourg, France. |
| Abstrakt: |
Microtubules are highly dynamic polymers of α,β-tubulin dimers which play an essential role in numerous cellular processes such as cell proliferation and intracellular transport, making them an attractive target for cancer and neurodegeneration research. To date, a large number of known tubulin binders were derived from natural products, while only one was developed by rational structure-based drug design. Several of these tubulin binders show promising in vitro profiles while presenting unacceptable off-target effects when tested in patients. Therefore, there is a continuing demand for the discovery of safer and more efficient tubulin-targeting agents. Since tubulin structural data is readily available, the employment of computer-aided design techniques can be a key element to focus on the relevant chemical space and guide the design process. Due to the high diversity and quantity of structural data available, we compiled here a guide to the accessible tubulin-ligand structures. Furthermore, we review different ligand and structure-based methods recently used for the successful selection and design of new tubulin-targeting agents. |
