Proteoglycan Is Sugar-Specific

The proteoglycan bikunin has a defined sequence of sugar units in its polysaccharide chains, chemists at Rensselaer Polytechnic Institute, the University of Georgia, and Japan’s Chiba University report (Nat. Chem. Biol., DOI: 10.1038/nchembio.673). Proteoglycans are proteins ornamented with long, sulfated polysaccharide chains known as glycosaminoglycans (GAGs). Bikunin, a serine protease inhibitor used in Japan as a drug to treat pancrea­titis, is the simplest proteoglycan, with just one polysaccharide attachment site. Despite its relative simplicity, scientists have previously been unable to determine whether bikunin’s single attachment site plays host to a variety of polysaccharide chains or any specific sugar sequence. Robert J. Linhardt, I. Jonathan Amster, and coworkers purified and sequenced bikunin’s GAG chain using tandem mass spectrometry. They found that there are chains of various lengths but that the shorter chains are truncated versions of the longer ones. “Because the chains are different lengths, there are so many components in the mixture that none of the components would be intense enough to fragment” for tandem mass spectrometry, Linhardt says. But the team was able to separate the mixture enough so that each fraction had a small number of components with intense enough peaks for the mass analysis. The researchers now plan to move on to more complex proteoglycans, Linhardt says.