Crucial to directing the active substances to the disease-relevant cells was the development of small chemical compounds that can bind disease-associated proteins to natural proteins present there, thereby blocking them. ‘We identified such molecules by Lego-like high-throughput conjugation chemistry’”, explains Min Zheng from the Structure-Based Drug Research Group at TU Darmstadt, who, as a chemist, played a key role in the project.

But intracellular complex formation was not the whole story: “A key additional finding was the ‘CellTrap effect’ that we discovered,” adds biochemist Christian Meyners, also from the Structure-Based Drug Research Group. “This is a general principle by which active substances are massively accumulated within cells.” This cellular accumulation enhanced the efficacy of the newly discovered compounds and allows the active substance to be directed specifically into diseased cells: “Prostate cancer cells exhibit higher levels of human FK506-binding protein 12 compared to normal prostate epithelial cells; we exploited this fact to direct a cytotoxic drug specifically to the cancer cells,” explains cell biologist Ahmed Bulldan from the Research Group on Systems Biology of the Stress Response at TU Darmstadt. And indeed: when both cell types were treated simultaneously, only the cancer cells died, whilst the healthy cells remained unharmed.
These experiments impressively demonstrate that the CellTrap effect represents a new and promising addition to the toolkit with which researchers can direct active substances precisely to where they are needed.

Researchers from Goethe University Frankfurt – which, like TU Darmstadt, is part of the Rhine-Main University Alliance (RMU) – were also involved in the study, as were the science and technology company Merck KGaA and the universities of Magdeburg and Trondheim in Norway.

The study emerged from the ProxiTRAPS and ProxiDIRECT projects within the BMBF-funded ProxiDRUGS Future Cluster, in which drug discovery researchers from the RMU and the wider Rhine-Main region have joined forces. The findings support the MoProX spin-off initiative, and the close collaboration with Merck will enable the widespread application of this approach in the development of innovative new medicines.