Self‐immolative (SI) spacers are sophisticated chemical constructs designed for molecular delivery or material degradation. We describe herein a (S)‐2‐(aminomethyl)pyrrolidine SI spacer that is able to release different types of anticancer drugs (possessing either a phenolic or secondary and tertiary hydroxyl groups) through a fast cyclization mechanism involving carbamate cleavage. The high efficiency of drug release obtained with this spacer was found to be beneficial for the in vitro cytotoxic activity of protease‐sensitive prodrugs, compared with a commonly used spacer of the same class. These findings expand the repertoire of degradation machineries and are instrumental for the future development of highly efficient delivery platforms.
Fast Cyclization of a Proline-Derived Self-Immolative Spacer Improves the Efficacy of Carbamate Prodrugs / A. Dal Corso, V. Borlandelli, C. Corno, P. Perego, L. Belvisi, L.L. Pignataro, C.M.A. Gennari. - In: ANGEWANDTE CHEMIE. INTERNATIONAL EDITION. - ISSN 1433-7851. - 59:10(2020 Mar 02), pp. 4176-4181. [10.1002/anie.201916394]
Fast Cyclization of a Proline-Derived Self-Immolative Spacer Improves the Efficacy of Carbamate Prodrugs
A. DAL CORSO
Primo
;L. Belvisi;L.L. Pignataro;C.M.A. Gennari
Ultimo
2020
Abstract
Self‐immolative (SI) spacers are sophisticated chemical constructs designed for molecular delivery or material degradation. We describe herein a (S)‐2‐(aminomethyl)pyrrolidine SI spacer that is able to release different types of anticancer drugs (possessing either a phenolic or secondary and tertiary hydroxyl groups) through a fast cyclization mechanism involving carbamate cleavage. The high efficiency of drug release obtained with this spacer was found to be beneficial for the in vitro cytotoxic activity of protease‐sensitive prodrugs, compared with a commonly used spacer of the same class. These findings expand the repertoire of degradation machineries and are instrumental for the future development of highly efficient delivery platforms.File | Dimensione | Formato | |
---|---|---|---|
Manuscript_post-print.pdf
Open Access dal 03/03/2021
Descrizione: Articolo principale
Tipologia:
Post-print, accepted manuscript ecc. (versione accettata dall'editore)
Dimensione
654.96 kB
Formato
Adobe PDF
|
654.96 kB | Adobe PDF | Visualizza/Apri |
anie.201916394.pdf
accesso riservato
Tipologia:
Publisher's version/PDF
Dimensione
3.18 MB
Formato
Adobe PDF
|
3.18 MB | Adobe PDF | Visualizza/Apri Richiedi una copia |
Pubblicazioni consigliate
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.