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UGA scientists team up to define first-ever sequence of biologically important carbohydrate
Date:10/18/2011

ntities of protein for study.

Carbohydrates, however, are a bit messier. Scientists don't fully understand how cells create them, and a given proteoglycan exists in multiple forms that are similar but not quite the same.

The researchers chose the simplest known GAG proteoglycan, a compound known as bikunin that is used in Japan for the treatment of acute pancreatitis, for their study. Of course, simplicity is a relative term: the sugar is composed of up to 55 distinct carbohydrate rings, which means that there are 210 billion different sequence possibilities. Previous studies performed over the past five years by the researchers that identified common sequences within the carbohydrate decreased the expected number of sequences to a mere 43 million.

Past attempts to sequence proteoglycans have relied on the so-called "bottom up" approach in which scientists use enzymes to chop a molecule into its component parts and then try to put it back together, like a puzzle. Using an alternative approach known as the "top down" method, the scientists placed the compound into high-powered mass spectrometers in both the Amster and Linhardt labs that allowed them to break the compound in predictable places. With larger puzzle pieces to work with, the scientists were able to deduce the structure of bikunin.

"Now that we have demonstrated that bikunin, a small chondroitin sulfate proteoglycan, has sequence, we are moving on to larger, more structurally complex dermatan sulfate and heparan sulfate proteoglycans," said study co-author Robert Linhardt, professor at Rensselaer Polytechnic Institute. "These show important biological activities in development and in cancer, and we are optimistic that our sequencing approach will work here as well."

Like all groundbreaking scientific discoveries, the finding actually raises more questions than it answers. Amster explained that the addition of sulfate to the sugar, for example, could in principl
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Contact: Sam Fahmy
sfahmy@uga.edu
706-542-6049
University of Georgia
Source:Eurekalert

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