New boron-containing chemical group is 10,000 times more stable than its predecessors

Chemists boost boron’s utility.


Thanks to its many traits, Boron, a metalloid element can be used as a drug component. In a past study, scientists have shown that boron-containing compounds’ stability can be increased by appending Benzene.

Using the same approach, scientists have created a modified version of a drug called Darunavir, a protease inhibitor used to treat HIV/AIDS. They found that this molecule bound to HIV protease much more tightly than the original version of darunavir.

In a recent study, MIT chemists have designed a boron-containing chemical group that is 10,000 times more stable than its predecessors. This new approach can incorporate Boron into drugs and potentially improve the drugs’ ability to bind their targets.

During tests, scientists found that the approach could improve the protein-binding strength of a drug used to treat diseases caused by the misfolding of a transthyretin protein.

To design this chemical group, scientists used carboxylate to anchor Boron within a molecule. An oxygen atom in the carboxylate forms a strong covalent bond with Boron.

Ron Raines, the Firmenich Professor of Chemistry at MIT, said, “That covalent bond pacifies the Boron. The Boron can no longer react with an oxygen molecule in the way that Boron in other contexts can, and it still retains its desirable properties.”

“One of those desirable properties is the ability to form reversible covalent bonds with the target of the drug. This reversibility could prevent drugs from permanently locking onto incorrect targets. Another useful feature is that the boron-containing group — also known as benzoxaboralone — forms many weaker bonds called hydrogen bonds with other molecules, which helps to ensure a tight fit once the right target is located.”

After finding the stability of Benzoxaboralone, scientists decided to create a molecule that can bind to transthyretin. Drugs that bind to transthyretin can stabilize it and prevent it from clumping.

Raines said, “Benzoxaboralone may offer medicinal chemists a useful tool that they can explore in many different types of drugs that bind to proteins or sugar molecules.”

Scientists are now working on a new version of darunavir that incorporates benzoxaboralone.

Raines said“We are working hard on this because we think that this scaffold will provide much greater stability and utility than any other presentation of boron in a biological context.”

MIT has filed for a patent on the use of benzoxaboralone in medicinal chemistry and other areas. The research was funded by the National Institutes of Health and the National Science Foundation.

Journal Reference:
  1. Brian J. Graham et al. Boronic acid with high oxidative stability and utility in biological contexts. DOI: 10.1073/pnas.2013691118
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