29 June 2016

Protein Constructor: details

Russian scientists create medicinal compounds-designers

"Science in Siberia"

The research group of the Institute of Bioorganic Chemistry of the Russian Academy of Sciences, led by corresponding member Sergey Mikhailovich Deev, suggests making medicines from a set of particles, just as we create different figures from a LEGO constructor.

Deev.jpg
Photo by Ekaterina Pustolyakova

Therapy and diagnosis are combined in a new medical approach called theranostics. S.M. Deev shared his successes in this area at the forum "Biomedicine-2016", held in Novosibirsk Akademgorodok. The term "theranostics" appeared relatively recently, in 2002. The Greek words it consists of reflect the essence of the medical approach: therapeia (treatment) and diagnostikos (able to recognize). This area can be called rapidly developing: already in 2015, more than 2,400 publications were devoted to it.

Theranostics implies targeted delivery of the compound (that is, the effect of the drug on cells with a certain molecular portrait) and the identification of specific pathological cells on their surface that distinguish them from healthy ones.

One of the main goals of theranostics is the search for universal tools for treatment. This is necessary, for example, because in oncological diseases, cancer cells mutate quickly and the selected medicine ceases to work. Diagnostic and therapeutic complexes should preferably be created from a set of complementary modules. This will allow you to quickly change the composition of the drug, that is, practically switch to individualized medicine: "You will not have to go through a long difficult path every time and re–form compounds using genetic engineering or chemical transformations – it will be enough blocks that can be assembled like a LEGO constructor," explained SM Deev. 

The research group led by S.M. Deev took two proteins as the basis for the platform: barnase and barstar, which create a strong complex with each other. One of the proteins attaches to a molecule that is focused on finding a target, for example, an antigen on a cancer cell, the other to a toxic or fluorescent molecule or nanoparticle.

According to S.M. Deev, among the latter, magnetic ones can be called the most promising. When they accumulate in the tumor, they perform a therapeutic function, their heating by an external electromagnetic field can lead to the destruction of cancer cells, besides they have the ability to focus in the focus of the disease. Scientists in the laboratory of S.M. Deev have created multifunctional compounds consisting of magnetic particles coated with barnase, fluorescent ones with barstar, and anti-cancer mini-antibodies with barnase.

Scientists have already used more than a dozen different cytotoxic agents and six types of nanoparticles. In most cases, the barnaza-barstar complex has proved to be a reliable module that allows you to assemble a variety of design options, and in one agent you can combine elements that are different in action.

The main problem was the retention of nanoparticles in the body: "We set the task to try to create biocompatible particles that can be injected into a person," S.M. Deev said. Animal experiments have shown that correctly sized particles are safely removed from the body in two months.

Another area that scientists are working on is the use of riboflavin (vitamin B2) for photodynamic therapy. When irradiated with blue light, it generates active oxygen radicals, which kills cancer cells. The problem is that the penetration of blue light through the skin is extremely inefficient. To solve it, scientists use nanophosphores, which, under the influence of the infrared spectrum, begin to emit blue. Accordingly, the combination of riboflavin with such nanoparticles leads to the suppression of tumors.

"Such experiments open up many possibilities. Time will tell how modest they are, and how promising they are, but this is the area of theranostics that is currently undergoing its rapid development," S.M. Deev summed up.

Portal "Eternal youth" http://vechnayamolodost.ru  29.06.2016

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