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Archive for Monday, October 22, 1990

STUDY OF MOLECULES SEEN AS AID IN DRUG DEVELOPMENT

October 22, 1990

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In a small laboratory on the fourth floor of Kansas University's Malott Hall, Jeffrey Aube and his staff are conducting research which may have a significant impact on future developments in medicine.

Aube, an assistant professor of medicinal chemistry who also teaches in the School of Pharmacy, is studying how the three-dimensional shapes of molecules affect their properties. He was recently awarded a prestigious Eli Lilly and Co. grant for this study.

The Lilly grant is awarded nationally to three chemists for $10,000 a year for two years. Last year a Lilly award went to Thomas Engler, an assistant professor in KU's chemistry department.

"For two awards to go to KU in two years is really amazing," Aube said.

Molecules, according to Aube, may be mirror images of each other, but that does not mean that they are identical. Instead, they come in left-handed and right-handed forms.

IN EXPLAINING this property, Aube uses a hand-and-glove analogy. While the left hand is a mirror image of the right, a left-handed glove will not fit the right hand correctly. Likewise, molecules can be mirror images but different.

"We're interested in this property and how to make molecules only left-handed or right-handed," he said. "This is where the connection to the drug industry and human health comes into it."

This left-handedness or right-handedness can affect the way molecules react to each other, and that includes molecules of DNA, enzymes, protein and antibodies, he said.

"These all exist in the human body as only a one-handed form (left or right)," he said.

Additionally, this "handedness" can have an impact on how drugs interact with other molecules in a person's body, according to Aube.

"Drugs have very different properties depending on if they're left- or right-handed," he said. "The right-handed (version) might have a property you want, and the left-handed (form) might not have any activity at all or, even worse, an activity that is different than what you want.

"THEY CAN make a difference, but they don't always. . . A lot of time it's not going to make any difference, but you can't count on that."

As new drugs have been developed over the past 10 to 20 years, this factor is being taken more seriously. It's all part of understanding the way drugs do what they do, he said.

"Nowadays in drug development, people are taking care to pay attention to this property," he said.

Aube emphasized that he and his staff are not drug designers. Instead, they are interested in creating chemical reactions, and the results of these studies he hopes will prove useful to other fields, including those professionals developing drugs.

"We want to make it easy to make right-handed molecules if that's what's needed or left-handed molecules, so this issue's no longer an obstacle," Aube said. "Right now it's hard to do and expensive.

"We're like an architect, adding a few more tools in the tool basket."

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