This current project focuses on synthetic functional systems that are relevant for the life sciences.  The general objective is find conceptually innovative ways to enter cells.  A universal method to deliver unmodified substrates in covalent form would be best.  To achieve this, we would like to learn how to grow transporters directly on substrates just before cellular uptake, and how destroy them right afterwards.  Cell-penetrating poly(disulfide)s are emerging as transporters of the future because their intracellular degradation should minimize toxicity and liberate the substrates.  Our lessons learned on ring-opening disulfide-exchange polymerization for the surface-initiated construction of multicomponent photosystems - very reliable, very robust - are currently applied to grow cell-penetrating poly(disulfide)s directly on substrates of free choice for their covalent delivery in native form.

With extensive proof-of-principle in hand, we currently focus on the growth of advanced cell-penetrating poly(disulfide)s (co-polymers, dynamic side-chain exchange, templated polymerization, templated side-chain exchange) as well as on substrate scope (fluorophores, proteins, antibodies, quantum dots, siRNA, genes, etc).

In an alternative approach, dynamic covalent chemistry is used to generate libraries of cationic amphiphiles for automated screening of siRNA delivery.  Because many of the hydrophobic tails are the odorants used previously to build an artificial nose, this approach is often referred to as fragrant delivery.

Methods:  This project offers minimal exposure to organic synthesis, even no synthesis at all if desired.  Much expertise in diverse biochemical methods can be gained.  All polymeric transporters are characterized by transport experiments in fluorogenic vesicles besides routine analytical methods (GPC, DLS, gel shift, etc).  Cellular uptake is initially characterized in HeLa cells (cell culture, flow cytometry, confocal microscopy, mechanistic probes, in close collaboration with the groups of Aurelien Roux and Howard Riezman).

Collaborations:  This is an NCCR project, realized in close collaboration with other members, including also NCCR group meetings, lectures, workshops, retreats, etc.  Interdisciplinary (post)doctoral studies in both chemistry and biology groups are possible.

Some recent references: J. Am. Chem. Soc. 2013, 135, 2088, J. Am. Chem. Soc. 2013, 135, 9295.