June 17, 2009
By: Jennifer Alexander
Note: This story originally appeared in the 2008 issue of Baylor Research magazine published by the Office of the Vice Provost for Research at Baylor.
Imagine enjoying the health benefits of a new medicine without suffering the unpleasant side effects that often come with it unpleasant side effects that often come with it.
This is one of the advantages that could result from research conducted by Drs. Kenneth and Marianna Busch with the help of funding from the office of the vice provost for research. The two professors co-direct Baylor's Center for Analytical Spectroscopy.
"Certain pharmaceutical, biological and organic compounds have a property referred to as 'chirality,'" says Kenneth Busch. "It comes from the Greek, meaning 'handedness' - it refers to molecules that are mirror images of one another, like your left and right hands."
The Busches, along with several graduate students, have been conducting chiral analysis. The data is obtained using conventional spectroscopic equipment including a fluorescence spectrophotometer that investigates how light interacts with matter. Data is then examined through the regression modeling of the spectral - or light - data.
Kenneth says the need to analyze these mirror-image compounds, known as enantiomeric pairs, arises from a trend in the pharmaceutical industry toward developing and marketing single-enantiomer drugs - the term used to describe one member of the pair.
The problem with trying to determine enantiomeric composition is that the enantiomers that make up the mirror-image pair have identical chemical and physical properties, making it very difficult to distinguish between the two. As a result, "You can't use ordinary chemical techniques," Kenneth says. To tackle this problem, they developed a simple method using guest-host chemistry to break the mirror-image symmetry of the pair, making them distinguishable spectroscopically.
"We take a sample, mix it with a chiral-host molecule, and it forms a complex with the host molecule," Kenneth says. Because the two enantiomers interact slightly differently with the chiral host, it modifies their spectral signatures, or the way they interact with light. As a result of this technology, "we can build regression models that permit us to predict the enantiomeric composition of a sample from its spectral data."
This process is new in the field and is the subject of a pending Baylor patent application, one of many filed for various Busch projects. The results of their work on this subject may lead to additional patent applications.
The benefit of all this work is valuable to pharmaceutical companies who may want to market drugs made from the enantiomer that provides the healthy property instead of having the side-effect-inducing enantiomer that tags along.
Companies need to show that once an enantiomeric pair has been separated, the desired isomer won't suddenly revert to the undesired isomer. Once that's been achieved, Kenneth says an advantage of this procedure they envision is for it to be automated. Speed is essential for companies hoping to put new drugs on the market quickly.
Former graduate student Jemima Ingle, who received her PhD from Baylor in 2006 and is now a National Science Foundation Postdoctoral Fellow at North Carolina A&T State University, found her role in the research focusing on making the analysis method more palatable to industry researchers. Ingle came to Baylor in 2001 after hearing Kenneth speak about his work because, she says, "I could understand it."
Ingle says previous research students laid the basic foundation of the technique, so she was able to concentrate on optimizing it. "My job was to address some issues with the technique, to make it more user-friendly," says Ingle.
The original studies involved samples of equal concentration, something Ingle says is difficult to achieve in a real-world setting; instead, she performed a study using varying concentrations. "It was a fascinating project," Ingle says. The additional research possibilities that developed made it "hard to find a stopping point."