When researching new drugs, not only is their efficacy important but also their ability to actually reach their intended targets in the body. After all, drugs that strike directly at the heart of the disease can be administered in lower dosages and thus have fewer side effects. In collaboration with colleagues from the University of Birmingham, for the first time Professor Eva Freisinger, Professor Roland Sigel and their team from the Institute of Chemistry were able to show that a synthetic, cylindrical molecule specifically recognizes a certain point in ribonucleic acid (RNA).
“RNA is the key to innumerable processes in living cells,” explains Sigel. One of its crucial functions in the cell is the transformation of genetic information into proteins, which makes it an interesting target for drugs. One characteristic structure of RNA molecules is the so-called three-way or Y junction. “For the first time, we were able to show that this cylindrical molecule fits perfectly into these three-way junctions, thereby stabilizing it,” explains Freisinger. Consequently, this was the first proof that a common RNA structure, the three-way junction, can serve as a target for the recognition of a designed metal complex.
This structure-based recognition has great potential as this cylindrical metal complex might well have anti-cancer properties. It reduces mitochondrial activity, the so-called powerhouses of the cell, inhibits the cell cycle and increases the cell mortality rate without damaging the genetic material. The use of such compounds, which can influence RNA, also opens up major possibilities for the treatment of other diseases. For instance, there is an urgent need to find new drug targets for autoimmune diseases or drug resistance.
Siriporn Phongtongpasuk, Susann Paulus, Joachim Schnabl, Roland K. O. Sigel, Bernhard Spingler, Michael J. Hannon, and Eva Freisinger. Binding of a Designed Anti-cancer Drug to the Central Cavity of anRNA Three-Way Junction. Angewandte Chemie, Int. Ed. 2013. Doi:10.1002/anie.201305079
University of Zurich