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JoAnne Stubbe’s free radical chemistry

“Nature has figured out how to control these radicals in an exquisitely specific fashion,” says Stubbe. Her breakthrough in understanding how free radicals and enzymes work together is being used to treat cancer.

JoAnne Stubbe is a chemist at MIT, and winner of a 2009 National Medal of Science. She’s been studying molecules called free radicals. These sorts of molecules carry only one electron – that’s a tiny charged particle – and most molecules need two electrons to be stable, Stubbe explained.

JoAnne Stubbe: In general, free radicals – molecules with an unpaired electron – are highly reactive, out of control, and react non-specifically with whatever they hit.

In other words, free radicals try to steal electrons from nearby molecules. When this volatile reaction happens in the body, it can end up causing cancers. But, JoAnne Stubbe has found that certain chemicals use free radical chemistry in a healthy way – in the case of her research, a human enzyme called ribonucleotide reductase, or RNR.

JoAnne Stubbe: Enzymes are proteins, made from amino acids, that are responsible for catalyzing all the reactions in our bodies. Without these enzymes, there would be no life.

She said that RNR is a special kind of enzyme. It helps create the building blocks for our genetic code, DNA – the famous double helix molecule inside every cell. Dr. Stubbe found that this special RNR enzyme puts the free radicals to work, helping to build the double helix.

JoAnne Stubbe: Nature has figured out how to control these radicals in an exquisitely specific fashion.

Stubbe’s breakthrough in understanding how free radicals and enzymes work together is being used to treat cancer.

Dr. Stubbe described the essential role that enzymes play in life. She said that’s because enzymes catalyze – or bring about a chemical reaction – for every material in our body.

JoAnne Stubbe: What’s amazing is that enzymes have two properties that have fascinated chemists forever. They can increase rate of reaction by a million fold, relative to the reaction with no catalyst at all. The second thing is they’re highly specific. That is, they only work on a single substrate. If your substrate was a sugar, it couldn’t work on an amino acid or a fat, for example.

Stubbe said the enzyme she studied, ribonucleotide reductase or RNR, converts the building blocks of RNA into the building blocks of DNA. It’s hard chemistry, she said, and that’s why it’s amazing that enzymes have evolved to use free radicals.

JoAnne Stubbe: We’ve discovered completely novel chemistry that nobody has ever seen before, which plays a central role in metabolism and is central for all life. Based on our discoveries, potent inhibitors of this enzyme have been rationally designed and used clinically. It would be important if you had pancreatic cancer because you would be taking one of the drugs that inhibit ribonucleotide reductase.

Lindsay Patterson

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