Unique screening method simplifies identification of novel drugs
A unique method to measure how effectively DNA building blocks are made, can be used as a starting point to find novel drugs against resistant bacteria as well as cancer. Already when a potential drug lead is identified this novel method, which is presented in the scientific journal PNAS, also pinpoints how the substance may inhibit cell division – thereby facilitating further development of the drug.
The two researchers who present this new knowledge are Fredrik Tholander, PhD in Medical Biochemistry at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, and also affiliated to Stockholm University, and Britt-Marie Sjöberg, Professor in Molecular Biology at the Department of Biochemistry and Biophysics, Stockholm University.
New DNA building blocks need to be constantly produced for DNA synthesis and cell division to work correctly. The enzyme that provides these building blocks is called RNR (ribonucleotide reductase) and is an obvious target for antiproliferative substances, like anticancer drugs and antibiotics. But as the enzyme is experimentally difficult to handle, there are only a few approved anticancer drugs that inhibit RNR, an enzyme that was discovered in the 1950s by the Swedish scientist Peter Reichard.
The new screening method is based on a variant of the well-known PCR (polymerase chain reaction) method and can be used in high-throughput screens to identify novel drug leads. Amongst other things, the two researchers have identified substances that kill Pseudomonas aeruginosa, a drug-resistant pathogen that causes hospital acquired infections as well as life-threatening infections in patients with cystic fibrosis.
Discovery of antimicrobial ribonucleotide reductase inhibitors by screening in microwell format.
Proc. Natl. Acad. Sci. U.S.A. 2012 Jun;109(25):9798-803