Β-Glucuronidase triggers extracellular MMAE release from an integrin-targeted conjugate. Issue 19 (25th April 2019)

• Record Type: Journal Article
• Authors: López Rivas, Paula; Müller, Christoph; Breunig, Christian; Hechler, Torsten; Pahl, Andreas; Arosio, Daniela; Belvisi, Laura; Pignataro, Luca; Dal Corso, Alberto; Gennari, Cesare
• Is Part Of: Organic & biomolecular chemistry. Volume 17:Issue 19(2019)
• Page Start: 4705
• Page End: 4710
• Publication Date: 2019-04-25
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/c9ob00617f
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : A non-internalizing conjugate targeting αv β3 integrin inhibits the proliferation of integrin-expressing cancer cells in the presence of β-glucuronidase. Abstract : A non-internalizing αv β3 integrin ligand was conjugated to the anticancer drug MMAE through a β-glucuronidase-responsive linker. In the presence of β-glucuronidase, only the conjugate bearing a PEG4 spacer inhibited the proliferation of integrin-expressing cancer cells at low nanomolar concentrations, indicating important structural requirements for the efficacy of these therapeutics.