Jenna Wilson talks to Jan Reedijk about the cisplatin-induced kink in DNA, anticancer chemistry, and playing the organ.   

Jan Reedijk is a professor of chemistry at Leiden University in The Netherlands. His research interests are coordination and bio-inorganic chemistry, in particular focusing on metal-containing drugs, homogeneous catalysis and molecular materials.

 

Your current work focuses on platinum anticancer chemistry. What does this involve?

In the 1960s, Barnett Rosenberg rediscovered the use of cisplatin as a successful cytostatic drug. Since then, a lot of new and exciting chemistry has resulted from several laboratories. Our work focuses on improvements to the chemical mechanism of action of cisplatin. This has led to controlled hydrolysis, transport and binding of the platinum species to DNA, with the majority of it binding at neighbouring guanine bases. This chelation causes a distortion of the DNA, which changes its interaction with proteins. Although the distortion is small, it is significant enough for the DNA not to be recognised by repair enzymes in tumour cells.
Using this style of mechanistic knowledge, several new types of compounds have been developed. We have focused on platinum compounds with a side arm. These were initially made to follow the pathway of the platinum species in the cell. Now we have compounds with a side arm that are also intrinsically anticancer active.

How did you become interested in this area?

It was a project that I started over 25 years ago in my previous job at Delft University of Technology. A PhD student had obtained an individual grant for anticancer chemistry and asked me if I would be willing to supervise his work. At the time, I was investigating the use of heterocyclic ligands with other metals. We combined the project with platinum and published our first papers on platinum anticancer chemistry in the late 1970s. After that, I moved to Leiden, where I was able to really expand the topic, thanks to intense collaboration with colleagues in Leiden.

What else are you working on?

We work on molecular magnetic materials and ion exchange materials. In addition, we have a number of projects involving biomimetic chemistry on structurally unusual compounds, and also projects on homogeneous oxidation catalysis. All our work has transition metals in common along with coordination chemistry of, in many cases, heterocyclic ligands.

If you could go back into the lab tomorrow, what experiment would you do?

I have been asked that question many times and each time I have a different idea. Sometimes I want to do molecular life sciences, sometimes molecular materials. Right now I am highly interested in constructing rigid molecular architectures from coordination building blocks and trying to do catalysis with them.

What achievement are you most proud of?

I am very proud of each completed PhD project. To mention one, our group was the first to discover that platinated-DNA contains a kink. This is caused by the chelation of cisplatin, but it remains double stranded which leaves most of the base pairing unchanged. At the time, almost nobody believed us. It was later proved to be true, which gave us a great sense of achievement.

What do you find most rewarding about being involved in academic research?

Academia allows a lot of freedom, which is something that I enjoy. However, what is most rewarding for me is that each year I receive new talented students. I find myself in a position where I can try to shape and polish them and give them hints to forward their careers. That gives me a lot of satisfaction.

What message do you have for young scientists?

Gorlaeus, the founder of science in Leiden, after which our lab is named, published a statement for young people, which I like to quote - 'on the way to finding the truth, never forget that your teacher is your biggest enemy.'
So, my advice is to try to be unconventional and do not always believe your teachers or the literature!

If you weren't a scientist, what would you do?

I would be a musician; I love to play the organ. When I was finishing high school, I had to decide between music and science. Fortunately, I learnt early enough that I am not technically good enough to make it as a professional organ player!