To find solutions to some of the major health challenges in the future, it is necessary to delve into the very smallest parts of what humans and the world are composed of. The foundation must be laid at the atomic level in order to understand and develop the antibiotics of the future. With the new NMR equipment, researchers now have an opportunity to focus sharply on cells, proteins, molecules and other building blocks that humans and the world are made of.
This contributes with greater knowledge about what happens when we try to kill diseased cells, and makes it easier to study which pieces should be put together in the research-related puzzle required to create an alternative to antibiotics.
The downside of the miracle calls for alternatives
Penicillin was something of a miracle cure at the time it was discovered. Mortally ill people could suddenly be cured of infections. However, the miracle cure turned out to have a downside. While penicillin and other antibiotics still cure sick people every day, more and more bacteria are developing resistance to them.
Scientists at the Interdisciplinary Nanoscience Centre (iNANO) are carrying out research into a possible alternative. AMPs – the abbreviation for antimicrobial peptides – can potentially become the miracle cure of the future as bactericidal agents, and they even have the fantastic advantage that bacteria cannot become resistant to them. The ultimate objective of the research is a personalised medicine. To achieve this, however, much greater knowledge is required about how AMPs work on the cells and how they can be used to create medicine.
The goal is personalised medicine
“The idea of creating personalised medicine – or rational drug design as it is also known – is to use some of the knowledge we already have to pinpoint exactly where we need to look for components of the medicine. We can’t try out five billion different AMPs to find out how to make them stable in the stomach, for example. We have to apply some of this knowledge so we can design the variant we need,” says Professor Thomas Vosegaard, who is head of the AMP research at iNANO.
NMR heads in the right direction
To acquire this knowledge, the researchers need to widen their understanding of the way AMPs work. They do this by combining existing knowledge with new observations and measurements. It is this accumulation of knowledge that the NMR spectrometer supports. The spectrometer is two to three times as sensitive as the equipment the researchers have previously had access to. The wealth of detail will therefore be much better and the measurements more precise. This could be compared with a gigantic magnifying glass with a zoom function that makes it possible to focus sharply right down to the atomic level and thereby detect some finer details. NMR is good at seeing how one thing interacts with another, which makes it ideal for characterising substances. “NMR removes your blindfold, so you can suddenly see what’s going on,” says Professor Vosegaard.
AMPs – promising challenge
AMPs are found naturally in a wide range of organisms, and there are therefore numerous variants. They exist in snails, fungi and plants, as well as in a number of primitive organisms. They are part of the immune system in the animals or plants in which they are found, and their main purpose is to kill bacteria.
Where penicillin works in a very advanced way by entering diseased cells and changing the function of a specific protein, AMPs work completely differently. They attack the cell membrane – a kind of fat layer surrounding the cell that keeps it all together. Proteins are complicated molecules with specific functions, but they can mutate and thereby become resistant to penicillin. The cell membrane is much more primitive and cannot mutate, so bacteria have no chance of developing resistance to AMPs. This makes AMP research a ‘hot’ field for scientists.
Unfortunately, there are lots of challenges associated with AMP research. These include the fact that they are not as specific as antibiotics, and they do not hit individual cells alone. Neither are they easy to get into the body because they are immediately broken down in the stomach. A much better understanding is therefore required of the way in which their potential can be utilised.
NMR provides new knowledge
Professor Vosegaard is pleased about the research-related opportunities he and his colleagues have gained with the inauguration of the NMR spectrometer.
“I believe in AMPs because their modes of action are so simple. They just destroy the cell. Working with them isn’t simple, but the effect is,” he says. “But we’re very focused on the fact that we need quite a bit more knowledge about AMPs. We’ll eventually use this knowledge to design some new substances that can be used for medicine,” adds Professor Vosegaard.
Source: Aarhus University