Person attributes
Karl Barry Sharpless is an American chemist and two-time winner of a Nobel Prize in chemistry. Karl Barry Sharpless was born in 1941 in Philadelphia, PA, USA. He earned his Ph.D. in 1968 from Stanford University and is a W.M. Keck Professor at Scripps Research, La Jolla, CA, USA.
The Sharpless Lab research is focused on developing useful reactivity and methods for controlling chemical reactions. Click chemistry, developed by the Sharpless Lab, is a set of reliable, selective reactions for rapid synthesis of new compounds through heteroatom links (C-X-C). Sharpless’s research group discovered CuAAC, the copper-catalyzed azide-alkyne cycloaddition, which is known as quintessential click chemistry. Later, the research group discovered SuFEx as a click chemistry method. Click chemistry has applications in DNA sequencing technologies, materials science, and pharmaceuticals, as tools for the discovery of new biomolecules and basic research on cell functions.
Click chemistry is a method of designing pairs of molecules that react only with each other in an irreversible way. The molecules form a strong, covalent bond and can occur in mild solvents, such as water, and produce harmless byproducts. The “click” in click chemistry denotes the convenience and satisfaction of snapping molecules together like with a luggage strap connector, or like legos. Sharpless describes click reactions as being “spring-loaded” for a single trajectory. Click reactions have a high thermodynamic driving force and proceed rapidly to completion, producing a single product.
Another important aspect of click chemistry is that the desired molecules link with each other while not reacting with other nearby biological molecules. The inspiration for click chemistry came from nature and Sharpless’s observations that carbon dioxide is nature’s starting material to create chains of polymers that are formed in nature in water using a few carbonyl chemistry-based reaction themes. Nucleic acids, proteins, and polysaccharides are condensation polymers of subunits linked through carbon-heteroatom bonds. Sharpless followed nature’s lead in his strategy to search for substances that can be created by joining small units together through heteroatom links.
K. Barry Sharpless, Carolyn Bertozzi, and Morten Meldal were awarded the 2022 Nobel Prize for Chemistry for their development of click chemistry and bioorthogonal chemistry. As described, click chemistry is a way to link molecules together efficiently to produce reliable products. Bioorthogonal chemistry allows chemical reactions to occur in living cells. Sharpless first proposed the idea of click chemistry in 2001. Sharpless’s and Meldal’s research teams independently discovered that copper ions could be used to initiate a reaction between an azide molecule and an alkyne molecule. Bertozzi and her colleagues developed click reactions that didn’t require copper, which is toxic to living cells. This advancement allowed the technology to be used to track molecules inside living cells and to develop “clickable antibodies” as therapeutics.
K. Barry Sharpless won the 2001 Nobel Prize in Chemistry for his work on chirally catalysed oxidation reactions. The Nobel Prize was shared with William S. Knowles and Ryoji Noyori, recognizing their work on chirally catalysed hydrogenation reactions.
Dr. Sharpless is one of the scientific founders of Regenica Biosciences, a medical defense pharmaceutical company developing antidotes to counter bioterrorism. Sharpless’s research led to the development of pharmaceutical products in the areas of nicotinic acetylcholine receptor ligands and cholinesterase inhibitors and reactivators. Sharpless was involved in the synthesis of REG-001, an antidote that protects against exposure to various types of nerve agents.
