Scientists sequencefirst carbohydrate biopolymer

Scientists sequence the first carbohydrate biopolymer

4:29 AM, 17th October 2011
Scientists sequence the first carbohydrate biopolymer
Structure of the bikunin. The portion on the left corresponds to the sugar part of the molecule, the sequence of which was determined in the current study. The portion on the right corresponds to the protein part of bikunin.

NEW YORK, US: DNA and protein sequencing have forever transformed science, medicine and society. Understanding the structure of these complex biomolecules has revolutionized drug development, medical diagnostics, forensic science and our understanding of evolution and development. But, one major molecule in the biological triumvirate has remained largely uncharted: carbohydrate biopolymers.

Today, for the first time ever, a team of researchers led by Robert Linhardt of Rensselaer Polytechnic Institute has announced in the October 9, Advanced Online Publication edition of the journal Nature Chemical Biology the sequence of a complete complex carbohydrate biopolymer. The surprising discovery provides the scientific and medical communities with an important and fundamental new view of these vital biomolecules.

“Carbohydrate biopolymers, known as glycosaminoglycans, appear to be really important in how cells interact in higher organisms and could explain evolutionary differences and how development is driven. We also know that carbohydrate chains respond to disease, injury and changes in the environment,” said Linhardt, who is the Ann and John H Broadbent Jr ’59 Senior Constellation Professor of Biocatalysis and Metabolic Engineering at Rensselaer.

The first glycosaminoglycan sequenced was obtained from bikunin. Linhardt views the discovery of the structure of bikuin as the first step on the ladder to the discovery of the structure of more complex proteoglycans.

“In our efforts to sequence carbohydrate biopolymers we don’t yet know if the defined structure we observe for this simple protoglycan will hold for much more complex proteoglycans,” he said. But, looking for structure in more complex proteoglycans will be among the next steps in the research for Linhardt and his team. The search for structure could help put to rest a long-running debate in the scientific community as to whether complex carbohydrate biopolymers require a defined structure to function.

“These findings represent a new way of looking at these complex biomolecules as ordered structures,” said Linhardt.

To uncover the entire structure, Linhardt and his team, which was led by his doctoral student Mellisa Ly, borrowed a technique from the field of protein research called the proteomics top-down approach.

Linhardt used a mass spectrometer located in the Rensselaer Center for Biotechnology and Interdisciplinary Studies (CBIS) to make his initial discoveries, and had these results independently confirmed on a separate and higher-level spectrometer at the University of Georgia.

Beyond the technology it also took faith and determination. Despite being the most simple of proteoglycans, there were still 290 billion different possible sequences for the molecule. “The first sample we looked at, we got the structure,” said Linhardt. “In the end we did 15 chains and they all came back playing the same exact symphony.”

The research is funded by the National Institutes of Health. Linhardt and Ly were joined in the research by Tatiana Laremore of Rensselaer; Franklin Leach and Jonathan Amster of the University of Georgia; and Toshihiko Toida of Chiba University in Japan.

© Rensselaer Polytechnic Institute (RPI) News

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