Alberto Dal Corso studied chemistry at Università degli Studi di Milano, where he obtained his Ph.D. in 2015 with Prof. Cesare Gennari. He then joined the group of Prof. Dario Neri at ETH Zürich as a postdoctoral fellow. In 2018, he returned to Università degli Studi di Milano, where he is currently working as a research fellow. In 2019 he was awarded the Junior Prize “Organic Chemistry for Life Sciences” by the Italian Chemical Society. His research interests include the development of novel drug delivery strategies and the synthesis of ligands for clinically relevant protein targets.
New-generation Self-Immolative Spacers for Fast and Controlled Release of Anticancer Drugs
Self-immolative (SI) spacers are covalent constructs capable of undergoing a spontaneous disassembly starting from a stable and inactive state, in response to specific stimuli . The growing interest in the generation of stimuli-responsive devices has led to the widespread application of SI spacers in different areas, including synthetic and analytical chemistry, material sciences, and medicinal chemistry, especially in the context of prodrugs, antibody-drug conjugates, and several other drug-release strategies. We have recently described a proline-derived 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. Starting from these findings, novel derivatives of this proline-derived SI spacer have been designed and synthesized, either to further accelerate the drug release rates or to develop a first-in-class spacer for dual-controlled drug release. These findings expand the repertoire of degradation machineries and are instrumental for the future development of highly efficient delivery platforms.
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