Could the next generation of drugs have a heavy metal core?

Publication date
Friday, 18 Feb 2022
Dr Christoph Nitsche is standing outside amongst an avenue of green trees.

If you happen to find yourself at a barbecue with Dr Christoph Nitsche, you must ask him about heavy metal. No, not the head banging, air guitar type of heavy metal; the type you find on the periodic table. The reason it’s worth asking about is because this kind of heavy metal has an amazing range of potential uses, from fighting cancer to antibiotics.

As a medicinal chemist at the ANU Research School of Chemistry, it was Dr Nitsche’s hunt for better approaches for drug discovery that led him to an iridescent, rainbow-coloured heavy metal element called bismuth.    

“Historically you have two major types of pharmaceuticals,” he explains. “Small molecules like aspirin that are chemically synthesised. Then biologics such as hormones, antibodies or vaccines. Both types are very different and have substantial benefits and drawbacks.”

Dr Nitsche is currently investigating new ways to produce drugs within the goldilocks zone: peptides.

“Because peptides are in-between these two extremes, they can represent the best of both worlds.”

There is a catch though. Traditionally, peptides are shaped like long strings. And once they are inside your body, they don’t always stay together. To combat this degradation, chemists are working to twist peptide strings into new shapes.

“Once constrained, the peptide can’t wobble around anymore. It binds exactly where we want it to, and it isn’t recognized by other enzymes that might degrade it.”

And these constrained peptides can mean big business: “There are multi-million dollar deals now.”

This is where the heavy metal comes in. Along with ANU PhD Candidate Saan Voss, Dr Nitsche has discovered a new way to keep peptides constrained using only a single atom of bismuth.

Close up of hand holding the heavy metal element bismuth, showing a crystal structure and iridescent surface.
Dr Christoph Nitsche holding the heavy metal element bismuth

Dr Nitsche says that this method might make manufacturing of peptides much easier and cheaper.

“You don’t actually need a chemist anymore to make constrained peptides. All you need is bismuth, which isn’t expensive or difficult to get.”

This has potentially massive implications for peptide drug discovery, making it easier to screen for thousands of potential peptide drug candidates.

Dr Nitsche says using bismuth to constrain peptides may have other benefits, especially because the metal can undergo radioactive decay.

“Our peptides might have implications for anticancer therapy.”

In this type of targeted alpha-particle therapy, the peptide and the bismuth atom would work in tandem. The peptide would provide the key to unlocking the cancer cells, delivering the bismuth alpha emitter exactly where it needs to be.

Another potential benefit of using bismuth in constrained peptides, is to harness its antibacterial properties.

“Bismuth is already used in antimicrobial drugs with prospects as antibacterial resistance breaker. So, if we could combine the constrained peptide and the antibacterial activity of bismuth, we might have some very promising antibacterial agents of the future.”

If you ever do hear Dr Nitsche’s heavy metal story at a barbecue, you’ll understand how passionate he is about chemistry and its applications for medicine.

“With research like this, it is exciting to be at the beginning of something that could potentially have huge implications,” he says.

You might want to ask him what’s next.

But you’ll have to wait for an answer because “that’s another barbecue story”.

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