Valentina Ripa
Molecular modelling to investigate tubulin conformational dynamics driven by antimitotic agents.
Rel. Marco Agostino Deriu. Politecnico di Torino, Master of science program in Biomedical Engineering, 2019
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Abstract
Microtubules (MT) play key roles in cell mitosis and in particular they help to segregate chromosomes. For this reason, MT are a desirable target in cancer treatment for the inhibition of the unregulated tumoral cells division. In addition, several tubulin isotypes exist, each one having its own sensitivity to a specific drug and a different level of expression depending on tissues. This represents an important opportunity in drug design, which exploits the isotypes expression to study and synthesize highly specific drugs, having a greater affinity only for diseased cells and causing reduced systemic effects. Antimitotic drugs act by interfering with MT polymerization-depolymerization kinetics, but the molecular mechanisms responsible for the drug activity is still unclear.
These drugs can be classified according to their effects on MT dynamics
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