EXCITING research from a team at the University of Copenhagen, Copenhagen, Denmark, has revealed molecular details of enzymes known as histone deacetylases, which may help to identify specific histone deacetylase inhibitors as candidates for anticancer drugs.
Histone deacetylases are a group of 11 enzymes which affect gene expression via interaction with histones and aid cell growth, and therefore play a role in disease development. Inhibition of these enzymes prevents this cell division and development so they are often used as targets for clinically approved medicines; however, the nonspecific targeting of these enzymes with medicines may result in side effects in patients with cancer. Previously, researchers were not aware of the detailed interactions and molecular processes of histone deacetylases around DNA until the team from the University of Copenhagen devised a method to quickly gather this information.
The team synthesised a peptide to target the specific regions affected by anticancer medicines and used a new method to identify peptides, which they resynthesised at a greater volume and introduced to human cells. They found that the targeted histone deacetylases were also inhibited in living cells. The unoptimised peptide had a pronounced and potent effect in the cells, which surprised the researchers, who commented that an almost completely natural peptide such as this one would have required modifications to optimise its properties.
The achievements of the study hold great promise for future cancer medicines, as Prof Christian Adam Olsen, from the University of Copenhagen, summarised: “Our detailed insight into the enzymes’ interactions gained with the new method provide hope for the development of more specific histone deacetylase inhibitors with potential as drug candidates. This could bode well for the development of more sophisticated compounds for cancer therapy with fewer side effects.”