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Dissecting the ‘Undruggable’

By April 21, 2021No Comments

Sugar has been called “evil,” “toxic,” and “poison.” But the body needs sugars, too. Sugar molecules help cells recognize and fight viruses and bacteria, shuttle proteins from cell to cell, and make sure those proteins function. Too much or too little can contribute to a range of maladies, including neurodegenerative diseases like Alzheimer’s, inflammation, diabetes, and even cancer.

About 85 percent of proteins, including those associated with Alzheimer’s and Parkinson’s, are beyond the reach of current drugs. One critical and abundant sugar (O-GlcNAc, pronounced o-glick-nack) is found on more than 5,000 proteins, many of them considered “undruggable.” But now, researchers at Harvard have designed a new, highly selectiveO-GlcNAc pencil and eraser — tools that can add or remove the sugar from a protein with no off-target effects — to examine exactly what these sugars are doing and, eventually, engineer them into new treatments for the undruggable.