Denying Sugar To Proteins Has Therapeutic Effects

Researchers have identified compounds that inhibit the enzymatic addition of the sugar fucose to proteins in mice, a process called fucosylation that plays a role in tumor progression, immunity, and inflammation (Proc. Natl. Acad. Sci. USA, DOI: 10.1073/pnas.1222263110). Nicole M. Okeley, Peter D. Senter, and coworkers at Seattle Genetics, Bothell, Wash., found the compounds by screening a library of fucose derivatives. Studies in mice show that one of the compounds, 2-fluorofucose, has anticancer and anti-inflammatory effects and enhances immunity. 2-Fluorofucose is the first compound shown to turn off fucosylation in living animals, suggesting possible therapeutic applications. It works in cells by inhibiting enzymes that add fucose to antibodies and other proteins. Among many possible effects of that inhibition is an enhanced antibody-based response to a vaccine. “We are evaluating this technology for potential clinical applications,” Senter says.