↵Better Medicine through Chemistry
Organic synthesis is a branch of chemistry that looks to make molecules, and the molecules we are building at Maynooth University are principally ones that are of interest to the pharmaceutical industry.
Identifying new potential drugs
The search is always on for new and more effective therapies for diseases.
We look to identify small molecules that have the potential to be therapeutic agents. Our work involves using computational models to screen large numbers of small molecules that could act as specific protein targets. Then we can build and test the most useful candidates in the lab.
A Sweet Spot in Biology
We think of carbohydrates as the starch in bread or the sugar we sprinkle on food, but in biochemistry, carbohydrates have many important roles in the body. We synthesise carbohydrate-based bioactive molecules and look at their functions - particularly how they are involved in regulating cells and in cell communication. The goals here are to develop new agents that can modulate the immune system, inhibit enzymes and act as anti-microbial agents.
Specific genetic molecules called oligonucleotides hold the potential for innovative new therapies. We are looking to develop RNA-based molecules that could affect the expression of specific genes and so have an impact on health. In particular we are interested in developing ways to ‘switch on’ these RNA-based molecules in the cell using light.
We want to improve the multi-step chemical reactions that are currently used to manufacture drugs - can we make them more efficient using asymmetric catalytic reactions? We have particular expertise in metal-free processes and in controlling the chirality of molecules, which is an important factor in the safety and effectiveness of an eventual active ingredient.
Homing Missiles for Tumours
Cancer cells display certain characteristics that tell them apart from healthy cells. We are developing responsive molecular systems that take advantage of this fact to target cancer cells only. We hope that this work will lead to new early stage cancer diagnostics and therapies that eliminate the toxic side effects seen by many modern day cancer treatments.
Pre-empting Antibiotic Resistance
Antibiotic resistance is a serious problem in the clinic: many antibiotic medications have lost their potency as microbes, and particularly the so-called ‘superbugs’ have developed mechanisms to resist the effects of the drugs.
We are looking at that evolution and developing approaches to predict and steer the microbial adaptation. This offers the opportunity to come up with strategies that could tackle resistance
before it arises
The Chemistry and Physics of Life
Biophysical chemistry combines aspects of biology, physics and chemistry - in particular it takes techniques and approaches normally used in physical chemistry and applies them to biological problems. It offers a new view on biology and at Maynooth University we have a strong emphasis on analysing why proteins are stable, how enzymes work and understanding the mechanical properties of biological tissue. With the use of computational biophysics techniques, we also look at protein dynamics, protein-protein interactions, biomolecular disorder, and at the effectsof post-translational modifications, such as glycosylation, as a modulator.
What makes proteins stable?
Proteins are the engines of life: they carry out varied and vital functions in and on cells. For a protein to function well though, it needs to have a particular shape and stability. If proteins become inappropriately unstable, either through changes to the protein itself or due to changes in the solution surrounding the protein, it can lead to a loss of protein function.
We have a strong interest in how proteins lose stability and aggregate. Cloudiness in the eye lens occurs in cataracts, and we are focusing efforts on understanding the process in genetic cataracts where proteins aggregate and form crystals in the lens that interfere with sight.
Protein stability is also of interest to the biopharmaceutical industry, which needs to control protein stability in manufacturing.
The Mechanics of Biology
Measuring the mechanical properties of biological tissues in situ is a challenge, but at Maynooth University we are working with collaborators at the University of Massachusetts Amherst to assess the mechanical properties of different regions of the eye.
Without functioning enzymes, life could not work as we know it. Enzymes allow important chemical reactions to happen in a timely fashion, and we can use them to artificially create important chemical agents.
At Maynooth University we have an interest in enzyme kinetics, particularly where enzymes require a metal ion to function. We have a strong research theme in binuclear metallohydrogenases, which function in bone and collagen resorption in the body, and in metallo-enzymes that could play a role in antibiotic resistance.
Inorganic Chemistry concentrates on the synthesis and behavior of inorganic and organometallic compounds, and at Maynooth University we have a particular interest in the development of metal complexes as therapeutic agents.
Metals have a long history in medicine - arsenic and silver compounds were weapons in the medical fight against infection before the advent of penicillin and other antibiotic compounds, and today silver is still used as an anti-microbial agent. Meanwhile, the platinum-based drug cisplatin has saved the lives of many cancer patients.
Our own work at Maynooth University focuses on developing silver-, copper- and manganese-based drugs as anti-cancer and anti-microbial agents.
We synthesise compounds and work with colleagues in Maynooth to screen their activity against potentially harmful microbes including Candida fungi, E. coli and MRSA. We also look at the effects of these transition metal complexes on cancer cells in the lab.
And as with any therapeutic agent, it’s important that it gets to the right place in the body to work effectively, so we seek to design ligands to attach to potentially therapeutic transition metal complexes in order to boost targeting to particular cells.