A spoonful of sugar . . .

Research into complex sugars involved in cell communications could have therapeutic value, Dr Paul Murphy tells Dick Ahlstrom

Your house is probably full of sweets and Christmas pudding and lots of sugary things, but they won't include the kind of sugars being made by Dr Paul Murphy. The University College Dublin chemist is synthesising the specialised sugars that support vital communication links between living cells.

Murphy is a senior lecturer in the school of chemistry and chemical biology at UCD and is a principal investigator at the €26-million Centre for Synthesis and Chemical Biology. Funding came from the Higher Education Authority's (HEA) Programme for Research in Third Level Institutions.

The new centre involves the work of 37 research investigators from UCD, the Royal College of Surgeons in Ireland and Trinity College Dublin.

"In the centre we work on wholly new molecules, new compounds that are interesting in terms of their biological properties," Murphy explains.

The challenge is to isolate a molecule of biological interest and then find ways to duplicate or synthesise the molecule so it can be tested for its biological effects.

"People are isolating a lot of compounds from natural products and doing analysis of their biological action. Of small molecule therapeutics, 50 to 60 per cent come from natural products or substances closely related to natural products," says Murphy.

His own work focuses on sugar molecules. They are true sugars, carbohydrates, but are very complex compared to what most of us understand as sugars.

"Everyone has heard of glucose, but these sugars are more complex," he says. "They coat cells and are involved in communications between cells. These sugars also mediate recognition between bacteria and their cell hosts."

Researchers are interested because of the therapeutic potential associated with them, Murphy says. Cuban researchers last year developed one of the first carbohydrate vaccines against meningitis and there is great potential for many more.

Scientists have been slow to exploit this potential however because the technology wasn't there to do so. There are machines that can now copy out sections of our genetic blueprint, DNA, and produce small biomolecules called peptides, but synthesising complex sugar molecules is very difficult, he says. "The technology hasn't been there to deal with the carbohydrates."

DNA and peptides, short chains of amino acids, are very regular structures, he says, but these sugars can have "huge diversity" even though they produce the same biological effect. "To produce a pure glycoprotein is very difficult."

The body has no difficulty synthesising the complex sugars it needs and relies on enzymes, the body's own nanomachines, to install sugar components on proteins.

Murphy received a €1.2-million award from Science Foundation Ireland to fund research looking at angiogenesis, the process that forms blood vessels. Sugars seem to moderate angiogenesis and have been shown to inhibit the development of endothelial cells, the cell type that lines the insides of blood vessels.

He is also looking at "imino sugars" which are similar to glucose but have a nitrogen in the molecule replacing an oxygen. They have a range of interesting biological effects including being able in some cases to inhibit enzyme activity. They can also imitate peptides despite being completely different in form and shape, Murphy explains.

An imino sugar structure is created and then small amino acid "side chains" are attached. When presented to a cell the imino sugar performs just like the original peptide but is much more stable and longer lasting because of its tough sugar-based structure.

It has been a good year for Murphy who earlier this year won an Astellas USA Foundation Award. Recipients are chosen after nominations from internationally-distinguished scientific colleagues, and then are invited to make a formal application to the foundation.

A small financial award comes with the prize, enough to support the work of a PhD student who will work with Murphy on carbohydrate chemistry in the Centre.