Structure-Uptake Relationship Study of DABCYL Derivatives Linked to Cyclic Cell-Penetrating Peptides for Live-Cell Delivery of Synthetic Proteins.

Autor: Saha A; Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Haifa, 3200008, Israel., Mandal S; Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Haifa, 3200008, Israel., Arafiles JVV; Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Robert-Rössle-Strasse 10, Berlin, 13125, Germany., Gómez-González J; Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Robert-Rössle-Strasse 10, Berlin, 13125, Germany., Hackenberger CPR; Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Robert-Rössle-Strasse 10, Berlin, 13125, Germany.; Department of Chemistry, Humboldt Universität zu Berlin, Brook-Taylor-Str.2, Berlin, 12489, Germany., Brik A; Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Haifa, 3200008, Israel.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2022 Nov 21; Vol. 61 (47), pp. e202207551. Date of Electronic Publication: 2022 Oct 19.
DOI: 10.1002/anie.202207551
Abstrakt: Modifying cyclic cell-penetrating deca-arginine (cR10) peptides with 4-(4-dimethylaminophenylazo)benzoic acid (DABCYL) improves the uptake efficiency of synthetic ubiquitin (Ub) cargoes into living cells. To probe the role of the DABCYL moiety, we performed time-lapse microscopy and fluorescence lifetime imaging microscopy (FLIM) of fluorescent DABCYL-R10 to evaluate the impact on cell entry by the formation of nucleation zones. Furthermore, we performed a structure-uptake relationship study with 13 DABCYL derivatives coupled to CPP to examine their effect on the cell-uptake efficiency when conjugated to mono-Ub through disulfide linkages. Our results show that through structure variations of the DABCYL moiety alone we could reach, at nanomolar concentration, an additional threefold increase in the cytosolic delivery of Ub, which will enable studies on various intracellular processes related to Ub signaling.
(© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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