Molecule targets DNA donut to stop cancer cells dividing
Cancer is essentially just cells that have gone rogue and are dividing unchecked, and now Australian researchers have designed a new molecule that may put a stop to that. It targets a protein called proliferating cell nuclear antigen (PCNA), a donut-shaped structure that plays a key role in cell division, which could lead to a new class of cancer treatments.
PCNA plays a vital role in the body. The protein repairs or replicates strands of DNA as they slide through the hole in the middle of the "donut," allowing cells to divide. But, sticking to its regular MO, cancer has a tendency to hijack this mechanism to help it grow out of control.
"PCNA is required for DNA replication and is therefore essential for rapidly dividing cancer cells," says John Bruning, lead researcher on the project. "If we can inhibit the action of this protein, the cells can't make DNA, so they can't divide. This is really tackling cancer at ground zero. It's stopping cell division and therefore tackling cancer at its most fundamental level."
For the new study, researchers from the Universities of Adelaide and Wollongong developed a molecule that can inhibit the function of PCNA. To do so, they took a fragment of a protein that interacts with PCNA, and altered its chemistry to amplify its effect and protect it from degrading in the body.
The molecule isn't the first to target the protein, but according to Bruning it is the first to be built from peptides. The team then conducted fluorescent polarization experiments to track how well the molecule interacts with PCNA, and found that it was stronger than other compounds described by other research teams.
"Because of the special approach we have used in turning a natural protein into a drug-like molecule, it fixes to PCNA more readily and its action is specific to this protein," says Bruning. "This is a first. It's the first in this type of inhibitor and it will pave the way for a new class of drugs inhibiting the proliferation of cancerous cells."
There are other potential advantages to this kind of treatment. About 90 percent of cancers overexpress PCNA, meaning the molecule could potentially help treat a wide range of cancer types. Plus, the protein doesn't mutate very often, so it's unlikely that it will develop a resistance to these drugs.
The research was published in Chemistry, A European Journal.
Source: University of Adelaide