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Long road to building a better painkiller gets boost at U of S synchrotron

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The dream is a big one: making opioid painkillers that are less addictive and adapting opioids into other medicines such as antibiotics and cancer treatments.

That dream is still years away from becoming reality. But it's one important step closer after groundbreaking research at the Canadian Light Source (CLS) at the University of Saskatchewan.

Dr. Ken Ng, a professor at the University of Windsor and adjunct professor at the University of Calgary, and Sam Carr, a PhD student from the University of Calgary, worked with Peter Facchini’s group at the University of Calgary to better understand how natural opiates are produced.

They focused on the enzyme codeinone reductase (COR), which is used in the last stage of opiate production in poppies. The researchers used the CMCF beamline to map out a 3D structure of COR.

They found that part of its structure is unique compared to related enzymes. Armed with this blueprint, they can start to modify that structure to change the enzyme's properties.

However, enzyme engineering is hard to do, Carr said.

"We have a three-dimensional structure and we can start looking at where things are, and try to change things and what happens is that we change things and it doesn't really do what we thought it would. So it's a very iterative process."

Still, knowing COR's structure has already allowed the team to make a small, successful change to how it works.

"I think it's misleading if people expect, 'oh, we'll have a better form of morphine in five years' or something. That's almost guaranteed not to happen," Ng said.

"But by understanding these things, at least you have a start towards changing these things in ways that you can't really do in a poppy or natural plants that make these kinds of drugs."

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