Breakthrough Understanding of Biomolecules Could Lead to New and Better Drugs

There’s a certain type of biomolecule built like a nano-Christmas tree. Called a glycoconjugate, its many branches are bedecked with sugary ornaments.

It’s those ornaments that get all the glory. That’s because, according to conventional wisdom, the glycoconjugate’s lowly “tree” basically holds the sugars in place as they do the important work of reacting with other molecules.

Now a biochemist at Michigan Technological University has discovered that the tree itself—called the scaffold—is a good deal more than a simple prop.

“We had always thought that all the biological function resides in the sugar,” said Tarun Dam, principal investigator of the Mechanistic Glycobiology Lab at Michigan Tech. “People didn’t appreciate that the scaffolds were active.”

The discovery opens up new avenues for research, in particular the development of more and better pharmaceuticals. Glycoconjugates are found naturally in the body, but they are also an important class of drugs that includes anything from cancer treatments to vaccines.

To determine if the scaffold had a role to play in biological reactions, Dam and his team built and tested two types of glycoconjugate molecules. They had the same sugars and virtually identical shapes but were comprised of different scaffolds, one made of protein, the other a synthetic. The scientists then tested how the different glycoconjugates reacted with biomolecules called lectins. Lectins play an important role in numerous biological processes and are a target for many glycoconjugate drugs.

If the scaffolds had been inert, the reactions would have been identical. However, the sugars on the protein scaffold reacted with the lectins differently.

“If the scaffolds are different, they can cause my drug to work one way and your drug to work another way, even though they have similar epitopes [sugars],” Dam said. “Tweaking the scaffold can change the drug’s function.”

An article on their study, “Significant Other Half of a Glycoconjugate: Contributions of Scaffolds to Lectin-Glycoconjugate Interactions,” was published in the July 15 edition of Biochemistry. In addition to Dam, the coauthors are Michigan Tech chemistry graduate students Melanie Talaga, Ni Fan, Ashli Fueri and Rob Brown; Yoann Chabre and René Roy of the Université du Québec a Montréal; and Purnima Bandyopadhyay, a research assistant professor of biological sciences at Michigan Tech. Dam is an assistant professor of chemistry at Michigan Tech. The study was supported by Michigan Tech and the Natural Science and Engineering Research Council of Canada.

Michigan Technological University is a public research university founded in 1885 in Houghton, Michigan, and is home to more than 7,000 students from 55 countries around the world. Consistently ranked among the best universities in the country for return on investment, Michigan’s flagship technological university offers more than 120 undergraduate and graduate degree programs in science and technology, engineering, computing, forestry, business and economics, health professions, humanities, mathematics, social sciences, and the arts. The rural campus is situated just miles from Lake Superior in Michigan's Upper Peninsula, offering year-round opportunities for outdoor adventure.