Proteasome Inhibitors with Photocontrolled Activity

Mickel J. Hansen, Willem A. Velema, Gerjan de Bruin, Herman S. Overkleeft, Wiktor Szymanski*, Ben L. Feringa

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

41 Citaten (Scopus)

Samenvatting

Proteasome inhibitors are widely used in cancer treatment as chemotherapeutic agents. However, their employment often results in severe side effects, due to their non-specific cytotoxicity towards healthy tissue. This problem might be overcome by using a photopharmacological approach, that is, by attaining external, dynamic, spatiotemporal photocontrol over the activity of a cytotoxic agent, achieved by the introduction of a photoswitchable moiety into its molecular structure. Here we describe the design, synthesis, and activity of photoswitchable proteasome inhibitors. Substantial differences in proteasome inhibitory activity in cell extracts were observed before and after irradiation with light. The presented results show potential for the development of chemotherapeutic agents that can be switched on and off with light, constituting a new strategy for spatiotemporally modulating proteasomal activity.

Originele taal-2English
Pagina's (van-tot)2053-2057
Aantal pagina's5
TijdschriftChemBioChem
Volume15
Nummer van het tijdschrift14
DOI's
StatusPublished - 22-sep-2014

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