Chemistry
A key to new drugs
Tiny metal-containing building block might become the core of new drug molecules.
A collaboration between research teams in Germany and the USA furnished a new concept for discovering drugs to treat life-threatening illnesses such as cancer, influenza, or multidrug resistant bacteria. The team proposes that three-dimensional metal-containing molecules may function as new building blocks. By adding additional functionality, these metal-containing building blocks can be developed towards drug molecules, as described by the teams of Professor Nils Metzler-Nolte from Ruhr Universität Bochum (RUB) and Professor Seth Cohen from the University of California at San Diego (UCSD). The teams report their work in the January 15, 2020 issue of Chemical Science. The paper is also highlighted as “Pick of the week”.
New key for different locks
The special feature of the metal-containing molecular building blocks in this work is their three-dimensional shape. Most organic compounds that form drugs on the market today are either linear or flat. “Think of these molecular building blocks like keys that need to fit in a keyhole. Most keys today are flat and only will fit in ‘conventional’ locks. But for other locks we need keys of different shapes.”
Metal centers with ligands
The unique three-dimensional shape of those molecular building blocks originates from central metal ions which are connected in all three dimensions to organic molecules, or so-called ligands. This allows the metal-containing molecules to bind to biomolecules important for treating illnesses.
Shaping the key blanks
Some considerations were important for the choice of the metal-containing building blocks. They should not be too big so as to be versatile enough to interact with a multitude of different targets initially. Then, they should have sites for further functionalization so as to eventually make them specific for a certain biological target. “Our compounds are not yet drug molecules by themselves” explains Nils Metzler-Nolte. “Rather, we are presenting a concept of how to reach a wider chemical space in shorter time, that will enable discovery of new drugs in the future.” This is just like a locksmith would shape a key blank to make it fit a specific lock, in this case one that cannot yet be opened with the conventional, flat keys. “We hope that in 8-10 years time, some of these building blocks would find their way into new drugs that are providing life-saving cures for human health” says Seth Cohen.