Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.
Skip to main content

Who we are:

We are a group of 10 - 15 medicinal chemists, the exact number continually changes as we often have visitors who join our group for only a few months. Our group contains PhD and Masters students, as well as experienced research scientists. Although we are all chemists, we all have experience of working at the interface of chemistry and biology.

We come from all over the world, and have worked and lived in many different countries. What unites us is our passion for learning, our love of discovery, and our commitment to help uncover secrets of biology that may one day have an impact on human health.

Our aims:

Our aim is to make molecules that have a specific well defined effect on human cells. Human cells contain many different types of molecules, each doing a highly regulated job that contributes to the health and survival of the cell. An important type of molecule found in cells are proteins. These act as highly specified machines, with each different type of protein performing a specific task such as breaking down food, or repairing damaged DNA. We aim to make molecules that will interact with a just one type of protein and stop it doing its job correctly, we call this type of molecule an inhibitor. By inhibiting a single protein, biologists can understand how the job of that protein effects the behaviour of overall cell.  Imagine a recipe for making a chocolate cake, you would assume that all the ingredients are doing something important, or they wouldn’t be there. However, to really understand what effect a single ingredient is having on the overall cake, you’d have to make the cake without including that ingredient. If you made a cake without baking powder, you would quickly learn that its job is to make the cake rise. The inhibitors our group designs allow biologists to see what cells look like when the type of protein that our inhibitor is interacting with isn’t performing its specified role.  This leads to a better understanding of both healthy and diseased cells, and may one day lead to new drugs.

How we make our inhibitors:

We spend most of our time working in a chemistry lab making inhibitors. This involves the careful mixing, stirring, and heating of chemicals in order to create the inhibitors we desire. Once they are made, we need to carefully purify our inhibitors to remove any trace of contaminants. This is important for performing biological experiments. If we give an impure sample to some cells, and we see a change in the cells' behaviour, we have no idea if it’s our inhibitors or an impurity that has caused the change. Therefore we spend a lot of time purifying the inhibitors that we have made.

We also have to make sure that the inhibitors we have made is exactly the one we were planning to make. Usually if we mix two chemicals in a flask, we can predict with reasonable certainty what product we will get. However, sometimes chemical reactions can give you a different product to what you predicted. Therefore it’s important to double check that we have made the molecule we were planning to make. We do this using many different techniques, but the two most important are Nuclear Magnetic Resonance (NMR) spectroscopy, and Mass Spectrometry (MS). NMR spectroscopy tells us how a molecule behaves inside a magnetic field.  Working in the same way as an MRI scanner at a hospital, NMR spectroscopy can provide a lot of information about the identity and purity of a molecule. MS is a very sensitive technique that allows us to determine the weight of a single molecule of our substance. We can then compare this to the predicted weight of our inhibitor, which can be worked out by looking up the weights of the atoms that make our inhibitor. If the two weights are the same, and the NMR spectroscopy results are consistent with what we would predict for our inhibitor, we can be reasonably sure we have made the right thing. 

How we test our inhibitors:

Once we have made our inhibitor, we work closely with biophysicists in order to work out how strongly our inhibitor interacts with the desired protein. We call the strength of interaction the potency of the inhibitor. We test potency by using a sample of protein that has been removed from the cell. This is the simplest way to measure an interaction between an inhibitor and a protein, because there are no other cellular processes going on that might affect the measurements.

We will also check to see if our inhibitor interacts with other proteins. It’s not possible to test every type of protein found in a cell, as there’s just too many. So instead we pick out a selection of proteins most similar to the one we are interested in. If our inhibitor doesn’t interact with these proteins, we assume it is unlikely to interact with any others in the cell. We call an inhibitor that only interacts with the protein of interest a selective inhibitor.

Quite often after performing these tests we’ll find out that our inhibitor doesn’t interact strongly enough with the desired protein, or that it interferes with many other proteins as well as the one we want to inhibit. Then we will design a new inhibitor, which will normally be similar to the first one, but with a few slight changes that we predict will make it more potent and more selective. We normally require several rounds of testing and redesign before we deem our inhibitor selective and potent enough for biological experiments.

Conclusion:

We make molecules that interact with a single type of protein and stops it from doing its job, we call this type of molecule an inhibitor. We spend most of our time designing, making, and purifying these inhibitors, before working with other scientists to determine if they are selective or potent enough. We usually go through several rounds of testing and redesign to get an inhibitor that can be used in biological experiments. We hope that biologists will use our inhibitors to learn more about healthy and diseased cells, and that this will one day lead to new drugs that can be used to treat patients.