06:10am Tuesday 15 October 2019

Chemical biology work could help to develop better drugs for the treatment of cancer and Alzheimer's

In a paper published this week in the journal Nature Communications, the team reports insights on understanding the structure and function of large protein complexes in the body that are involved in the regulation of gene expression.

These complexes contain histone deacetylase (HDAC) enzymes, which alter how DNA is packaged within cells.

HDAC-IPHDACs are implicated in many different diseases from cancer to Alzheimer’s – and several drugs are in clinical use for the treatment of different types of lymphoma and myeloma.

The Leicester group previously discovered that HDAC activity in complexes is regulated by a small molecule called an inositol phosphate. The Bath group, led by Professor Barry Potter, has worked on inositol phosphates for some 25 years and a key question was to further understand the mechanism of activation.

Working with Leicester’s Departments of Molecular & Cell Biology (Professor John Schwabe) and Chemistry (Dr Andrew Jamieson), the group from Bath’s Department of Pharmacy & Pharmacology designed and synthesized a number of chemical biology tools, including a fluorescently-tagged derivative that allowed them to investigate how inositol phosphates and substrates bind to HDAC complexes and how the two sites communicate.

Barry said: ‘This work with Leicester colleagues illustrates wonderfully the power of interdisciplinary collaboration to solve major questions in biology.

‘It has been a fabulous journey using engineered chemical tools in concert with structural biology to unravel this important mechanism.’

University of Bath

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