Amphiphilic Polyphenylene Dendron Conjugates for Surface Remodeling of Adenovirus 5.

The arrangement of amphiphilic surface groups plays an important role in many biological processes such as protein folding or biorecognition. We report the synthesis of amphiphilic polyphenylene dendrimer branches (dendrons) providing alternating hydrophilic and lipophilic surface groups and one reactive enthynyl group at the core. The amphiphilic surface groups serve as biorecognition units that bind to the surface of adenovirus 5 (Ad5), which is one of the most common vectors in gene therapy. The Ad5/dendron complexes showed high gene transduction efficiencies in coxsackie-adenovirus receptor (CAR)-negative cells. Moreover, the dendrons offer incorporating new functions at the dendron core by in situ post-modifications even when bound to the Ad5 surface. In this way, we provide a new platform for introducing bioactive groups to the Ad5 surface without the necessity to chemically modify the virus particles. Moreover, we analyzed binding of blood proteins to surfaces coated with amphiphilic dendrons, which is essential to predict their performance in the blood stream and of high relevance for in vivo applications.