Bath combines biology and chemistry to thwart cancer drivers
University of Bath researchers are harnessing bacteria to develop millions of potential drug molecules inside living cells, in order to speed therapy development to combat hard-to-treat cancers.
Writing in Cell Chemical Biology they said their new technology can create libraries of peptide molecules, chemically stabilising them as they are tested inside the cell.
Peptides, which provide the building blocks of proteins are being investigated use against transcription factors that form highly resistant cancer drivers.
Each bacterium employed produces a different peptide, which can be chemically modified inside the living cell, locking the peptide into a defined shape.
First author Dr Andrew Brennan, from Bath’s department of Life Sciences, and Deprtment of Life Sciences, defined the approach as “a powerful way of letting biology and chemistry work together”.
“Some cancers are driven by transcription factors that are stuck in the ‘on’ position, causing cancer cells to grow and spread when they shouldn’t. This uncontrolled growth is what drives tumours to form and metastasise,” he explained.
Using a self-developed technique called the Transcription Block Survival (TBS) assay, the researchers screened the modified peptides’ activity. In order to survive, bacteria needed to produce a peptide capable of blocking the cancer-causing transcription factor.
“Our approach uses peptides to interfere with these faulty switches. What’s new is that we can chemically stabilise tens of millions of different peptides inside the cell while we test them, rather than doing this later in the lab,” said Brennan.
The department added that because the chemistry occurred within living cells, the approach was “cleaner, greener, and cheaper” than conventional peptide drug discovery, avoiding toxic solvents and multi-step chemical processes often involved in the lab. The simpler method also enhanced the opportunity to adapt the processes for larger-scale peptide production and manufacturing.
Professor Jody Mason, from Bath life science department and the Institute of Sustainability and Climate Change stated: “What excites us is that we’re not just finding peptides that bind a target, but peptides that are chemically stabilised, resistant to breakdown, and functional inside live cells.
“This opens up a completely new way to go after cancer targets that have long been considered undruggable.”
Pic: Chokniti Khongchum
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