Chemistry without orthodoxy

The Moscow Physics and Technical Institute (MIPT) has recently been seriously "carried away by the sciences of the living. On May 29-30, the IV International Conference of Fiztehbio was held there, where not only two Nobel Prize laureates performed-Michael Levitt and Robert Hubert, but also a scientist, seriously claiming- Valery Fokin , professor of the prestigious Skripps Institute in California (Scrips Research Institute), one of the best chemists of the decade according to Thomson Reuters, since last year, the head of the MFT with a laboratory of chemical synthesis and catalysis, which was opened with the means of the Russian government megagagant. The Correspondent of the TRV-HOW Aleksey Paevsky talked with a scientist about chemistry and life.

- Tell us how you came to medical chemistry?

-I am a chemist-organic chemist, but I have always been interested in the field of science at the junction of chemistry, biology and medicine, since school times. At that time, there were much less drugs: a thick volume with a small print, which is now called a “reference book of pharmaceuticals”, literally 20-25 years ago fit in a thin book. As they worked, it was not always described, and it was amazing for me: it seemed to me that everyone had to know everything. It turned out that everything is not so simple and obvious.

As a scientist, I started with organic synthesis, in particular, my dissertation was devoted to obtaining compounds with anti -inflammatory properties. When I started an independent career, it was interesting to swim a little against the current. You see, in recent years, science has become more complicated: we went into details, better understood cascades of biochemical reactions that take place in living organisms, and a mantra appeared: complex problems require complex solutions. And it seems to me that far from always the solution of complex problems requires complex and non -obvious solutions. Sometimes approaches, which at first, seem too simple to us, turn out to be the most effective. This is the interest - to understand how we can influence chemical and biological processes. My laboratory is engaged in such research: how to collect molecules with specified properties from fairly simple and affordable blocks A and B. And ideally I would like to watch chemical and biological processes in real time right in the body, if not with our own eyes, then with the “eyes” of molecular ones Reporters that we send to the body.

- How?

- One of the options is to use the chemistry that is unfamiliar to nature. All processes in nature are usually reversible: few reactions pass in only one direction. We have the opportunity to use completely different molecules or functional groups that we synthesize with our own hands. They are unknown to nature, so for her they are “transparent” or orthogonal, in the chemical sense of the word. They exist in a plane that is “indifferent” to nature. Therefore, such chemistry is often called bioortiononal.

Introducing such molecular reporters into proteins, carbohydrates, nucleic acids, lipids - any life molecules, we get the opportunity to observe them. The idea of ​​using such bio -native groups, as you see, is quite simple (and research in this area began long before our work).

But then deep serious chemistry begins: you need to understand which molecules meet these requirements and how we can use them by introducing them into biological materials, and, most importantly, how we can conduct chemical reactions to them. Although, at first glance, one of the reactions, which is now widely used in this area, is very simple - it is copper sulfate, ascorbic acid and two reacting azides and acetylene.

- How did the idea to open the laboratory in the MIPT arose?

- The chemical sciences were not the main direction of the educational and research activities of the physical education, although there were always departments dedicated to chemistry. The movement in the direction of studying living systems is quite obvious recently, it is happening in all education - if only because this area of ​​knowledge is still very empirical, despite the rapid development of the pharmaceutical industry and methods of medical diagnosis. We have learned to treat some diseases well, many - by pumpkin. And chemistry here plays an absolutely key role, because the “construction” of molecules - small, large, biological products based on proteins and nucleic acids, synthetic vaccines - requires reliable chemical reactions. For both research and industrial production. Chemists here act as designers and molecular architects who design and guaranteed to collect the necessary molecules when and where it is necessary, based on the understanding of the molecules of “building materials” and the required properties of the final substance.

Now the methods of computer molecular modeling are well developed quite well, and formation in this area on a physical education has always been on the forefront. In areas adjacent to biomedicine, thus the embodiment of the obtained models into real compounds requires knowledge in the field of chemistry. Thus, the development of chemical science on physical education became a necessity and was enthusiastically supported by the university administration.

- What did Fizteh attract you personally?

- I was here for the first time in the winter of 2012. Then there was no clear plan and specific financial support, but there was an obvious interest and the idea of ​​cooperation. I was lucky to meet then with students and applicants-high school students of FizTech-Lyceum. And these guys with such genuine interest and spontaneity listened to us that it was their burning eyes and inspired me. I perfectly understood that there were no bases for chemical research as such. But I knew that there is support for the biofarmklaster, the research institute of chemical diversity, is the interest of Fiztekh himself. And he decided to organize the laboratory here. Plus, the opportunity to start from scratch is a certain challenge and the opportunity to embody your vision in the form that you consider necessary. So it was an adventure, but in a good sense of the word. I want to say that there should always be a little healthy adventurism in science: if you do not take risks and make an obvious (read: boring) science, you can’t make big discoveries.

- What scientific tasks does the laboratory solve now?

- Now we are at the stage of formation - the synthesis of those “bricks” from which we will collect our biologically interesting compounds. Now my colleagues are engaged in chemical synthesis of compounds that contain orthogonal groups - these are azids and acetylene, new cyclic molecules that will be useful for obtaining ligands. One of the projects includes close interaction with Buldt and Cherezov laboratories: they are engaged in the research of membrane proteins receptors-the so-called GPCR receptors associated with G-beels (for opening in this area Robert Lefkovitz and Brian Kobilka received the Nobel Prize in Chemistry). To establish the structure of proteins, they must be clicked, and this is a very complex process. To do this, screening is carried out - crystallize immediately in a large number of different conditions. We, in turn, synthesize molecules that could, associated with this receptor protein, stabilize it in order to make it possible to study its crystalline structure. And this is an important fundamental and applied task. For example, endotheline receptors included in this class regulate the expansion and narrowing of blood vessels and pressure, and leukotrine receptors - allergic reactions and inflammatory processes. They are involved both in normal physiological and pathological processes - immune diseases, various kinds of inflammation, asthma. The establishment of the receptor structure will allow “turning on” and “turn off” its work by choosing suitable antagonists and agonists. This is just one example. In general, we hope to create a fairly universal chemical platform that will study complex biological processes that play a role in various diseases.

- How do you see the future work of the team?

-I would like that after three or four years a strong and independent scientific team to appear on the physical education, ready to develop and use unorthodox chemical approaches to solving various range of tasks. This would be the maximum task - to achieve the understanding that the solution of modern multifaceted problems is impossible “vertical” methods when ideas come only from the leader. They should be born among the researchers themselves, who should have academic freedom and not be afraid to try, take the initiative, make mistakes, and even with a bang to fall only in order to try something else. We must get away from planning in the style of “here is our plan for a year, and this week you must do this, this and this reaction, and if it doesn’t work out, then this one”. This approach will lead to a little, because he does not reveal the creative abilities of each student, graduate student and even a led researcher. If we can create such an atmosphere, the solution of many problems will be on our shoulder. And now, just four months after the start of work, we moved away from vertical planning. My colleagues are not waiting for my call, but work with their ideas. Of course, we want to get compounds that will be used in medicine, but this will happen only if qualified, independently thinking and working, slightly adventurous scientists appear. And the results of such a team will be required. The creative beginning is the most important part of the scientific process, we must regain children's spontaneity and greed in the search for something new-and not be afraid to make mistakes.

- What do you plan to do for chemical education in the MIPT?

-This is a very important task for us and our chemical colleagues-it is enough to radically improve chemical education in the MIPT and understand what subjects we can offer what students they can be useful and in what sequence. While these are an open type of lectures, no one received assessments in the setting for them, but soon such courses will be included in the MIPT educational program.

Photo by Alexei Paevsky