How did you get interested in Medicinal Chemistry?
I came first into contact with molecules that interfere with a biological system during a Biology lesson at school. Then we were tasked to write an assay-like text about antibiotics. A glimpse into lexica showed fascinating molecules and fascinating modes of action. This fascination never died, but shifted over the years to the question how to find such molecules in the first place.
Where and when did you obtain your PhD diploma?
I obtained my PhD in the group of Prof. Christa Müller (University of Bonn) in 2007. The topic of my PhD project was the design and synthesis of nucleotide mimetics as ectonucleotidase inhibitors.
Where did you have your postdoc positions?
In the groups of Prof. Christa Müller (University of Bonn) and Prof. Jonathan Hall (ETH Zürich)
Where are you currently working and what is your current position?
I am currently a research group leader at TU Dortmund University.
What are your current research interests?
My group is working on the technology of DNA-encoded screening libraries. Basically, we are wondering how to populate the chemical space of these libraries. Is there something like an ideal screening library? In the light of the theoretically synthesizable chemical space, design of screening libraries is a daunting and intellectually stimulating task. Yet, finding novel biologically active chemical matter on a challenging target is so highly rewarding.
What do you like best about your work?
The freedom to pick a scientific problem and the freedom to walk new ways to work on this problem. A fantastic aspect of a small molecule screening platform technology is that you can venture into many (though certainly not all!) biological targets.
What do you consider your greatest achievement in your scientific career?
There is not the one greatest achievement, but rather a gradual learning process how to combine best the different scientific disciplines required for library design, screening, and then the follow-up once a molecule has been identified.
Which of your papers are you most proud of and why?
Difficult to answer, but I would say they fall into the category of “first-time disclosures”, and they raise a lot of questions that need to be answered in further studies. I would pick the identification of a microRNA-lnc-RNA interaction by a chemical biology strategy (Nat Chem Biol, 2015), the demonstration that a certain DNA design enables a broad chemistry scope on oligonucleotide conjugated starting materials (Chem Sci, 2017), the observation that micelle-promoted catalysts enable on-DNA reactions (J Am Chem Soc, 2019), and the identification of TEAD-YAP inhibitors from a small, designed DEL (ACIE, 2020).
What are the features of a successful PhD student or postdoc?
Curiosity and passion, and a lot of discipline and affinity for the written word.
What is the most embarrassing thing you have done in the lab while doing experiments, e.g. explosions?
Nothing to report here. I am sorry. DNA and RNA do not explode, they die a silent death.
What are your recommendations for a book, podcast, website, blog, YouTube channel or film?
I enjoy reading the blog “In the pipeline” by Derek Lowe. A must-read is the book “In search of the magic bullet”.
Which scientist do you admire the most and why?
I would rather say that I am fascinated by the early era of drug research. How was it possible at all to venture into trying to cure disease with so little knowledge about physiology and toxicology, and they did not even have an NMR machine to fully and timely understand what they were making. Did nobody tell these researchers that drug research is impossible under these circumstances?
Which field of medicinal chemistry do you consider the most promising for the future?
I do not know whether it is the “most” promising field, but in my opinion the modulation of intracellular protein-protein interactions holds much promise, and with technologies that enable handling unprecedented chemical space - be it virtual or real - I hope we will witness more breakthrough stories in this field.
What would you like to ask from other medicinal chemists?
Don´t underestimate the impact of technologies but readily embrace them, and the value of innovative chemistry for compound design.