Constructing Hybrid Protein Zymogens through Protective Dendritic Assembly

• DOI: 10.1002/anie.201308533
• Publication Date: 2013-12-20T21:42:28Z
• Authors: David Y. W. Ng; Matthias Arzt; Yuzhou Wu; Seah Ling Kuan; Markus Lamla; Tanja Weil
• Keywords: Boronic acid

The modulation of protein uptake and activity in response to physiological changes forms an integral part smart therapeutics. We describe herein the self-assembly a pH-responsive dendrimer shell onto surface active enzymes (trypsin, papain, DNase I) as supramolecular protecting group form hybrid dendrimer-enzyme complex. attachment is based on interaction between boronic acid salicyl hydroxamate, thus allowing macromolecular assembly respond pH 5.0 7.4 highly reversible fashion. Catalytic efficiently blocked presence but quantitatively restored upon degradation under acidic conditions. Unlike native proteases, constructs are shown be taken up by A549 cells colocalized compartments. programmed intracellular release proteases induced cytotoxicity, thereby uncovering new avenue for precision biotherapeutics.