Daniel Blair Lab

Modifications in chemical reactivity or functionality can lead to pediatric diseases. Many approaches for making medicines have historically relied upon non-covalent interactions to target disease-causing biomolecules. Our laboratory strives to amplify or deactivate biological functions through the design of covalent chemical matter, which makes or breaks chemical bonds with disease-causing biomolecules. Leveraging the ability to make or break these bonds in a strategic, precise way may lead to new and innovative treatment methods for pediatric diseases.

Most antibiotics target ribosomes, the key piece of machinery that creates all proteins. There are promising hints that small, chemically reactive molecules may be effective for targeting ribosomes in treatment approaches. Forming new chemical bonds to ribosomes may prolong the action of a medicine at a particular molecular site. Expanding our knowledge in this area could lead to a strategy for revitalizing antibiotics that have diminished in effectivity due to their overuse. This research is the first step toward the creation of chemical matter that selectively and covalently targets RNA.

Another area of our laboratory’s research inquiry revolves around disulfide bonds and how the making or breaking of those chemical bonds can lead to a protein’s activation or deactivation. Disulfide bonds typically serve as the guardians of protein function. But their aberrant or malfunctional behavior underlies diseases like cancer and celiac disease, as well as disorders such as depression, and are integral components during viral infection. Despite this association of disulfide bonds and disease, we lack effective chemical matter for therapeutic intervention. Our goal is to create reactive chemical matter to intercept disulfide bonds with precise chemical reactions and to establish disulfide bonds as a new class of therapeutic target.