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Matthijs ten Cate (promotion date: 27 May 2004)

Self Assembled Receptors based on Hydrogen Bonds

Promotion Date: 27 May 2004

Mattijs ten Cate

The idea of the project is the development of receptors to recognize foreign substances, for instance medicines.
The financer, STW, was interested in a project enabling testing medicines outside the body, which decreases the use of laboratory animals. But receptors on ‘smart vesicles’ could also be deployed in the body to recognize for instance cancer cells,.

This is the ultimate purpose and the basic idea.

What is your thesis about?

The idea of the project is the development of receptors to recognize foreign substances, for instance medicines. The financer, STW, was interested in a project enabling testing medicines outside the body, which decreases the use of laboratory animals. But receptors on ‘smart vesicles’ could also be deployed in the body to recognize for instance cancer cells,.

This is the ultimate purpose and the basic idea.

If you look at antibodies you will find that they are comprised of four chains, and the bottom part of these chains are alike in every antibody. The top is comprised of a number of amino acids that vary, thus enabling recognition. On our hydrogen platform which is always constructed in the same manner we try to mount peptides or sugars that nature also uses to recognize other molecules. The system includes nine components, on three of which we mounted the peptides. By adding gas molecules the receptors assemble themselves from potential receptors in the library.

I take it that you have a chemical background?

Yes, I did analytical chemistry in Delft, and pharmaceutical chemistry in Amsterdam.

Do you work with all kind of medical groups?

No. The research is still at a very conceptual stage and it is still a long way from practical applications.

What was the main outcome of your research?

We established in what kind of environments or basic structure worked. With that knowledge we worked on the actual receptor systems, encapsulating molecules and binding gas molecules to the surface.

The problem was that our system still only functions in apolar solutions, like chloroform and bezene. The ultimate was methanol and even at that the structure became unstable. Water appeared to be a bridge too far. And of course for use in the body you need water, chloroform and benzene are obviously out of the question. But when you look at nature you see that all this kind of receptor reaction does not take place in water, but on the cell membrane or in the cell itself. That is how and why we developed the vesicle technique, artificial cells as it were.

The process of self assembly takes place in the membrane of the artificial cell.

What did you like best?

The development of the vesicles was very interesting. I went to work with a group in Geneva for that. The vesicles proved to be the solution for the problems we encountered in the first stages of the research and when I saw that the self assembly worked in the vesicle membrane I was really thrilled. And also the physics aspect of the research was new for me; I really liked gaining a deeper insight in thermo dynamics and that sort of thing.

Did you also go to conferences?

We had an ACS (American Chemical Society) meeting in Washington with the whole group, which is a very big symposium where I had a poster presentation. And there were several conferences in Europe.

Are you going to continue with pharmaceutics?

No, I applied with the Max Planck Institute in Berlin. It is the institute for colloids and interfaces. I will continue working with vesicles and super molecular structures.

I applied in December and I offered to write a proposal for the Alexander von Humbold Stiftung. Of course they agreed with that, but the outcome of this is not known yet.

Last week I went there to apply for a permanent position and it was democratically decided that I fitted socially and scientifically well within the team, so I got the job. Now it is only a matter of formalities.

I looking forward to work in such a renown institute and be a member of such a closely collaborating group, and Berlin I am told, is a very attractive city to live.

I would not know, I was four years old the last time I went there.

For the summary of the thesis, click here. (English and Dutch)