Page 8 - Tyrosine-Based Bioconjugations - Jorick Bruins

Preface
Preface
Summary for non-scientists
The most asked questions to us by non-scientists are along the lines of: “What do you research?” and “What purpose does your research serve?”. These are very important questions, and every scientist should be able to explain their research and importance in understandable terms.
I would like to do the same, and to do that I would like to explain the title ‘Tyrosine-Based Bioconjugations’, as the title often gives a very clear explanation of the contents. Let’s start with ‘bioconjugations’; this is a term used for any chemical technique that connects two (or more) molecules together, with at least one of these molecules has to be a “biological molecule”, such as proteins, sugars or DNA. In this thesis, we focus only on proteins.
Proteins are constructed by any combination of 20 different building blocks called ‘amino acids’. Differences between proteins can occur from different amounts of total amino acids, as well as differences in the order of building blocks. For example: haemoglobin, the protein that is present in the blood and allows us to bind the oxygen that we breathe. This crucial protein has 135 amino acids in a very specific sequence allowing us to, well.. live. Another protein, alcohol dehydrogenase, ensures that alcohol is broken down in the liver. This is an enzyme, which means it perform reactions by itself via catalysis, has 375 amino acids in a very different order to fulfil a completely different purpose.
About the amino acids. One of these amino acids is tyrosine, which is the key focus in our research. We were able to install extra tyrosine ‘blocks’ in proteins without them losing their function. Then, we used these tyrosine residues to do the bioconjugation, where we attached molecules to our protein of choice, like adding fluorescent groups!
Why were we doing this? Well, we used to connect to proteins called ‘antibodies’. These nifty proteins are comparable to a ‘heat-seeking missile’; each different antibody has a different target to which they bind, meaning they will stick to a specific target. Some of these antibodies can bind to cancer cells (for example Trastuzumab, also called Herceptin), whilst ignoring other cells. That is why we used our developed chemistry to bind very toxic molecules, used in chemotherapies or radiotherapies, to these antibodies. This created a system that can bring the chemotherapy straight to the cancer cells, whilst ignoring the healthy cells. This results in a lot less adverse effects.
These constructs are called antibody–drug conjugates, or targeted therapies. This field has been growing a lot over the past year. This thesis describes a new and promising approach to creating these medicines.
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