Details

Autor(en) / Beteiligte

• Ng, David Y. W.
• Arzt, Matthias
• Wu, Yuzhou
• Kuan, Seah Ling
• Lamla, Markus
• Weil, Tanja

Titel

Constructing Hybrid Protein Zymogens through Protective Dendritic Assembly

Ist Teil von

• Angewandte Chemie (International ed.), 2014-01, Vol.53 (1), p.324-328

Auflage

International ed. in English

Ort / Verlag

Weinheim: WILEY-VCH Verlag

Erscheinungsjahr

2014

Quelle

MEDLINE

Beschreibungen/Notizen

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