Prof. Andreas Hennig

Center for Cellular Nanoanalytics, University Osnabrück

Biocompatible and non-toxic macrocyclic host molecules such as cyclodextrins, calixarenes, and cucurbiturils provide the possibility to create interfaces between biomolecular and supramolecular stimuli-responsive systems, for example, for biosensing, membrane transport, and nanobioconjugation. The combination of macrocyclic hosts with fluorescent dyes provides supramolecular chemosensors for a variety of biologically relevant analytes with micromolar to picomolar affinities. Useful applications include, for example, the label-free, real-time fluorescence monitoring of enzyme activity.[1] When the self-assembled chemosensors are encapsulated in the aqueous interior of large and giant unilamellar vesicles, the membrane transport activity of various compounds can also be monitored by fluorescence in real time.[2] This includes the membrane translocation of cell-penetrating peptides, the activity of antimicrobial peptides and membrane protein pores, as well as membrane permeation of low-molecular weight drugs. Most recently, we have also shown that the sensitivity and selectivity of the supramolecular chemosensors can be largely enhanced by orders of magnitude with properly set up pH gradients across the phospholipid bilayer membrane.[3]

Proper synthetic modification of the host molecules affords amphiphilic derivatives, which dramatically increase the membrane activity of arginine-rich and lysine-rich peptides in vesicle-based experiments, enable enzyme-gated membrane transport, and afford an enhanced cellular uptake of these peptides into the cytosol of various cell lines by a direct translocation mechanism.[4]

Finally, current efforts and strategies to enhance supramolecular chemosensors and transporters will be presented.

[1] (a) Nat. Methods 2007, 4, 629; (b) Concept: Chem. Eur. J. 2012, 18, 3444; (c) Review: RSC Adv. 2022, 12, 10725-10748.
[2] (a) J. Am. Chem. Soc. 2019, 141, 20137; (b) Commun. Biol. 2020, 3, 383; (c) ACS Sensors 2021, 6, 175; (d) Review: Org. Mater. 2022, 4, 53-60: (e) Chem. Commun. 2024, in press.
[3] Angew. Chem. Int. Ed. 2022, 61, e202207950.
[4] (a) Angew. Chem. Int. Ed. 2017, 56, 15742; (b) Angew. Chem. Int. Ed. 2021, 60, 1875; (c) Chem. Eur. J. 2024, e202400174; (d) Review: Isr. J. Chem. 2024, in press.