Enhanced Live-Cell Delivery of Synthetic Proteins Assisted by Cell-Penetrating Peptides Fused to DABCYL.

Autor: Mandal S; Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, 3200008, Haifa, Israel., Mann G; Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, 3200008, Haifa, Israel., Satish G; Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, 3200008, Haifa, Israel., Brik A; Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, 3200008, Haifa, Israel.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2021 Mar 22; Vol. 60 (13), pp. 7333-7343. Date of Electronic Publication: 2021 Feb 22.
DOI: 10.1002/anie.202016208
Abstrakt: Live-cell delivery of a fully synthetic protein having selectivity towards a particular target is a promising approach with potential applications for basic research and therapeutics. Cell-penetrating peptides (CPPs) allow the cellular delivery of proteins but mostly result in endosomal entrapment, leading to lack of bioavailability. Herein, we report the design and synthesis of a CPP fused to 4-((4-(dimethylamino)phenyl)azo)benzoic acid (DABCYL) to enhance cellular uptake of fluorescently labelled synthetic protein analogues in low micromolar concentration. The attachment of cyclic deca-arginine (cR10) modified with a single lysine linked to DABCYL to synthetic ubiquitin (Ub) and small ubiquitin-like modifier-2 (SUMO-2) scaffolds resulted in a threefold higher uptake efficacy in live cells compared to the unmodified cR10. We could also achieve cR10DABCYL-assisted delivery of Ub and a Ub variant (Ubv) based activity-based probes for functional studies of deubiquitinases in live cells.
(© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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