By Mark Dwortzan
Large compounds that link repetitive sequences of sugar molecules in a chainlike pattern, polysaccharides are exploited as building blocks for cell structure, energy and communication. Impressed with their biological versatility and clinical potential, researchers have prepared polysaccharides that prevent blood clotting, treat cancer tumors and reduce arthritis symptoms. But prospects for further clinical breakthroughs are severely hampered by the inefficient methods used to synthesize these and related compounds.
Today it’s possible to assemble short sequences of less than 10 repeating sugar molecules in the lab, either by connecting the molecules together one at a time, or isolating a segment of a polysaccharide chain found in nature, but both approaches are tedious and result in compounds with a limited set of properties. A new method pioneered by Professor Mark W. Grinstaff (Chemistry, BME, MSE) and NIH postdoctoral fellow Eric L. Dane (Chemistry), however, promises to enable biomedical researchers to design and build much larger polysaccharide structures—consisting of 10, 50 or even 100 repeating sugar molecules—all in a one-step process.
A detailed description of the new method appeared in the August 31 edition of the Journal of the American Chemical Society.
“We have devised a way to prepare a polysaccharide of defined molecular weight (size) and composition,” said Grinstaff, noting that these two factors determine the number and types of properties exhibited by the compound, from biological activity to water solubility. “Our method may ultimately boost the performance and capabilities of polysaccharides that are currently in clinical use and lead to new biomaterials and drug therapies.”
To make possible the production of polysaccharides with up to 100 repeating sugar molecules, the researchers replaced the “ether linkage,” a structure that connects sugar molecules in natural polysaccharides, with an amide, the linkage used to connect peptides together to form proteins. Working with sugar molecules derived from glucose in the lab, they showed not only that they could use the method to synthesize long polysaccharides, but also that the resulting compounds could successfully mimic the behavior of natural polysaccharides in a biological assay.
“We view this as a new tool to make libraries of compounds to mimic properties of polysaccharides that have been identified in biological and clinical studies,” said Grinstaff. “Scientists can then use those compounds to design new biomaterials with additional properties that may be clinically beneficial.”