Russian scientists together with colleagues from Belgium with a substance — a prototype of personalized drugs against autoimmune diseases and cancer. The study is published in the journal Frontiers in Pharmacology.
The basis was taken the poison motley Scorpion Mesobuthus eupeus, can block potassium channels “gateway” for potassium ions across the cell membrane. These are essential to every cell elements are involved in many cellular processes, such as conducting nerve impulses, cell division and their interactions with each other, as well as in the immune response.
The activity of potassium channels it is possible to stop special substances, or blocking ligands, which cells lose their function or work properly. These are poisonous organisms to protect themselves or to immobilize prey, but their poisons can be used as the basis for creating drugs.
In different tissues of the body there are different types — isoforms — potassium channels that help the cell to function properly. Scientists from the Institute of Bioorganic chemistry named after M. M. Shemyakin and Y. A. Ovchinnikov (IBCH RAS) and the University of Leuven in Belgium studied blockers of particular isoforms of the potassium channel (Kv1.3), which is involved in autoimmune processes, and also necessary for the growth of malignant tumors.
Based on these medication may prevent the attack of immune cells on healthy human cells or slow the spread and growth of tumors. The work is executed at support of the grant of the Presidential program of research projects of the Russian science Foundation (RNF).
As the “molecular frame” to create a specific blocker was selected as one of the components of Scorpion venom, the molecule of which is a folded chain of several amino acids, or polypeptide capable of clogging potassium channels like a cork.
First, the authors modeled the interaction of the blocker with the channels on the computer. It turned out that, in the polypeptide molecule, it is possible to substitute some amino acids that the blocker lost the ability to communicate with other isoforms of potassium channels, with the exception of selected Kv1.3.
Next, the researchers received the modified polypeptide in the system of synthesis based on E. coli and have studied its ability to block potassium current through the membrane. As predicted by computer modeling, the new derivative showed a hundredfold increase in specificity to the Kv1.3 compared to the natural analogue.
“We have developed a new approach of design of polypeptide ligands on the basis of computer calculations. In the article, we can design and “transform” molecule, which initially did better on the Kv1.1, Kv1.3-selective ligand”, States the press-release words of the head of the project grant RSF Alexei kuzmenkova, researcher at the laboratory of molecular tools for neuroscience the Institute of Bioorganic chemistry.
Using the method of molecular design, the authors artificially changed the specificity of a component of Scorpion venom so that he began to only block the potassium channels responsible for the development of autoimmune diseases and cancer.
“Our global goal is to understand how the areas of interaction between peptide ligands and potassium channels. This will help to find the key to creating the next generation of drugs for personalized medicine,” — says Alexey Kuzmenkov.