Maytansinol is a valuable precursor for the preparation of maytansine derivatives (known as maytansinoids). Inspired by the intriguing structure of the macrocycle and the success in targeted cancer therapy of the derivatives, we explored the maytansinol acylation reaction. As a result, we were able to obtain a series of derivatives with novel modifications of the maytansine scaffold. We characterized these molecules by docking studies, by a comprehensive biochemical evaluation, and by determination of their crystal structures in complex with tubulin. The results shed further light on the intriguing chemical behavior of maytansinoids and confirm the relevance of this peculiar scaffold in the scenario of tubulin binders.

Maytansinol Derivatives: Side Reactions as a Chance for New Tubulin Binders / P. Marzullo, Z. Boiarska, H. Perez-Pena, A.-. Abel, B. Alvarez-Bernad, D. Lucena-Agell, F. Vasile, M. Sironi, K.-. Altmann, A.E. Prota, J.F. Diaz, S. Pieraccini, D. Passarella. - In: CHEMISTRY-A EUROPEAN JOURNAL. - ISSN 0947-6539. - (2021). [Epub ahead of print] [10.1002/chem.202103520]

Maytansinol Derivatives: Side Reactions as a Chance for New Tubulin Binders

P. Marzullo
Primo
;
Z. Boiarska;F. Vasile;M. Sironi;S. Pieraccini;D. Passarella
Ultimo
2021

Abstract

Maytansinol is a valuable precursor for the preparation of maytansine derivatives (known as maytansinoids). Inspired by the intriguing structure of the macrocycle and the success in targeted cancer therapy of the derivatives, we explored the maytansinol acylation reaction. As a result, we were able to obtain a series of derivatives with novel modifications of the maytansine scaffold. We characterized these molecules by docking studies, by a comprehensive biochemical evaluation, and by determination of their crystal structures in complex with tubulin. The results shed further light on the intriguing chemical behavior of maytansinoids and confirm the relevance of this peculiar scaffold in the scenario of tubulin binders.
maytansine binding site; maytansinol; microtubules; tubulin; tubulin binders
Settore CHIM/06 - Chimica Organica
17-nov-2021
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/890672
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