Sept 22, 2000
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THE UNIVERSITY OF VICTORIA Sept 22, 2000 |
 Some unconventional research may revolutionize how chemists search for new drugs
by Kirsten Rodenhizer “Can we do chemistry this way instead?” That’s the question UVic chemistry professor Dr. Tom Fyles is asking as he conducts some unconventional research funded by a two-year, $100,000 grant from the Canadian Society for Chemistry (CSC) The grant — sponsored by pharmaceutical companies AstraZeneca Canada, BioChem Pharma Inc., Boehringer Ingeleheim (Canada) and Merck Frosst Canada — will allow Fyles to explore the potential of doing automated chemical synthesis on gold surfaces instead of conventional polystyrene beads. In conventional chemistry, chemists do one specific reaction, then isolate the new compound they have created. Combinatorial chemistry is a means of making many chemical compounds at once, or substituting particular ingredients in a systematic way to create a library of new compounds. Combinatorial chemistry is most often done by machines, which are capable of conducting the many necessary reactions quickly and efficiently. Pharmaceutical companies use combinatorial chemistry as a way to discover “lead” compounds for new drugs. “What we do is create chemistry that is compatible with automated synthesis,” says Fyles. The CSC originally requested proposals to invent new chemical reactions that would expand the repertoire of such machines. Fyles decided to take a different approach, and proposed they change the very solid on which they were doing their reactions. They normally use polystyrene; he suggested gold. “It’s like inviting a bunch of interior decorators to fix up a room,” says Fyles. “I come along and say, I don’t even want to be in this room.” Until now, gold has commonly been used in tandem with sulphur compounds to create modified gold surfaces that are very stable. Most of the time, chemists who create such surfaces aren’t interested in doing more reactions on them — they create them for other tasks. For example, gold surface technology has been used in medical procedures such as blood and tissue-typing and genetic screening. However, Fyles plans to use these surfaces in a totally new way, doing chemical reactions on them and then isolating the new compounds by using electrons to release the new compound into a solution. “It sounds almost like magic but it’s really easy to do,” he says. “The whole premise is that the reaction step is better on gold than on polystyrene.” Many reactions don’t work on polystyrene because the compounds react with the polystyrene itself. Fyles estimates that out of the hundreds of thousands of possible reactions, only about 10 per cent can be done on polystyrene. “If gold works on at least another 10 per cent, it will be a great deal better, and it’s likely more,” he says. Surprisingly, gold powder is also cheaper to purchase than polystyrene beads. Fyles and his team are currently doing reactions one after the other to test whether surface technology is viable in combinatorial chemistry — a process that takes him back to his early days as a chemist. “I haven’t done this since the mid-’70s,” he says. “Most chemists don’t do reactions like this today. It’s become a specialty area because robots can do it faster.” Fyles is grateful that the companies who funded the grant were willing to take a risk on his unconventional proposal. “I really am delighted the companies took the view that they can afford to gamble,” he says. “ If we can create a new chemistry it would be great because it would give us a whole new class of reactions to do.” |