Promising molecular tool that target and inhibit cell immortality, Organic chemists at Northwestern University and his team have now developed a promising molecular tool that targets and inhibits one of the main mechanisms of cell permanence: the telomerase enzyme.
This enzyme is over-expressed in about 90% of human cancer cells and has become an important study site for cancer researchers.
Normal cells have the telomerase gene, which, however, is usually not expressed.
Telomerase is the main enzyme that makes cancer cells live forever, the researchers said. We want to connect this eternity. We have now designed the first of its kind as a small molecule that irreversibly binds to telomerase and stops its activity.
This mechanism offers a new way to treat cancer and understand cell aging.
Scheidt is a chemistry professor at Weinberg’s College of Arts and Sciences and professor of pharmacology at the Feinberg School of Medicine at Northwestern University. The big idea behind the design of small molecules comes from nature. Promising molecular tool that target and inhibit cell immortality.
A decade ago, Shade was interested in the biological activity of chloractomycin, which is produced by bacteria and has been shown to inhibit telomerase.
Scheidt and his team used chrolactomycin as a starting point for the design of their small molecules.
They produce more than 200 compounds over the years, and the compound they call NU-1 has been tested most effectively. The synthesis is very effective and takes less than five steps.
NU-1 inhibits telomerase unlike anything that has happened before, Shade said. This is done by forming covalent bonds.
Another advantage of NU-1 is that its molecular structure must allow scientists to add pressure as it is therapeutic.
All human cells have telomeres, short DNA sequences that cover the ends of each DNA strand. Your job is to protect our chromosomes and DNA. When cells divide, telomeres shrink until they can no longer do their work. Natural cell death occurs. Promising molecular tool that target and inhibit cell immortality.
In contrast, cancer cells with increased telomerase activity become immortal and reverse the normal telomere contraction process.
The telomerase enzyme replicates telomeres repeatedly and thus expands telomeres. The result is infinite cell division and immortality.
The famous HeLa cell, which was isolated from Henrietta Lacks’ cervical cancer tissue in the 1950s, is still divided.
Telomerase has been the target of cancer research for decades. In 2009, three scientists received the Nobel Prize in Physiology or Medicine for their previous studies on telomeres and telomerases.
After developing their new compound, Scheidt and his team initiated collaboration with Professor Stephen Kron of the University of Chicago and Scott Cohen of the Sydney Children’s Medical Research Institute to investigate the extracellular role of telomerase inhibition.
Studies have focused on how new compounds interact with telomerase at the molecular level and how inhibition of telomerase makes cells sensitive to chemotherapy and radiation. From this work, NU-1 rises to the top. Promising molecular tool that target and inhibit cell immortality. With the release of this study, we are testing the impulse of this extraordinary tool to see what it can do and learn more about telomerase, Shade said. We continue to improve it.
Research carried out in human cells. The next step, said Shade, is to make more effective connections and test it in animal models.