TSRI scientists receive $2.1 million NIH grant to create new library of drug candidates

Scientists at The Scripps Research Institute (TSRI) have received a grant of more than $2.1 million from the National Institutes of Health's National Institute of General Medical Sciences to create and screen a new library of drug candidates.

The researchers will use a branch of click chemistry--a method developed by TSRI Professor and Nobel laureate Barry Sharpless in the mid-1990s for quickly discovering new, or improving existing, chemical function. The new research could lead to novel therapeutics and improved positron emission tomography (PET) protocols for children with neurodevelopmental disorders.

"The idea is to make medicines that are more selective and more potent--letting us use a lower dose for the same effectiveness," said Sharpless, also W.M. Keck Professor of Chemistry and member of the Skaggs Institute for Chemical Biology at TSRI, who will be principal investigator on the four-year project.

TSRI Associate Professor Peng Wu, co-investigator on the new grant, added that the research will take advantage of powerful new gas-based click chemistry reactions developed by the Sharpless lab in 2014. The SuFEx--Sulfur Fluoride Exchange--reactions enable the team to link molecules of their choice together using derivatives of a common commercial chemical considered essentially inert.

"The molecules will only react when they find the right partner," said Wu.

The researchers will use these reactions to create potential "covalent drugs," a class of therapeutics that includes penicillin and aspirin. The team will then explore the molecules' reactivity in zebrafish to identify their potential as therapeutics.

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