On the initiative of Aleksandr Pozharsky, Professor of the Department of Organic Chemistry at SFedU, his students, Candidates of Chemical Sciences Vladimir Mikshiev and Aleksandr Antonov, together with scientists from the University of Wroclaw (Poland) and the Institute of Chemistry of St. that stabilize the helical structure of proteins. A publication about this appeared in 2020 in ChemPhysChem magazine with the status of Very Important Paper.
It is known that the basis of matter in the Universe is constituted by invisible elementary particles (electrons, protons, neutrons, quarks, etc.), presumably formed during the Big Bang. The fundamental law of nature is the continuous structuring and enlargement of material particles through various interactions. So, from elementary particles, mainly in the depths of stars, nuclei of chemical elements are formed, from which more and more complex molecules are then built. During this process, called chemical evolution, under favorable conditions (for example, existing on Earth), supramolecules are born, which include proteins, nucleic acids, polysaccharides and fats. A characteristic feature of supramolecules is their ability to self-organize and recognize other molecules. The structuring of supramolecules is the result of multiple weak (non-valence) interactions. In biology, one of the main non-bonded interactions is hydrogen bond. For example, hydrogen bonds form a double helix of DNA, as well as filamentary helixes of proteins (polypeptides) or crumpled into globules. The protein helix inside each loop is stabilized by NH… O = C hydrogen bonds between carboxamide and amide groups (Fig. 1).
Research on the fundamental characteristics of the amide group, such as the cis-trans isomerization barrier, resonance energy, or acid-base properties, continues from year to year due to its particular relevance. They are important for ensuring further progress in medicine, biology and biotechnology, chemistry and interdisciplinary sciences.
The main interests of the group of SFedU professor Alexander Pozharsky are non-classical types of hydrogen bonds. First of all, this concerns strong short hydrogen bonds. In recent years, the opinion has been established that it is they who are primarily responsible for the softness, speed, and selectivity of most biochemical reactions.
Proton sponges and their analogs have become successful models for such studies.
The significance of the phenomenon of the so-called proton sponges, discovered in 1968, is that for the first time organic molecules were synthesized capable of slowing down the rate of proton transfer by a factor of millions and using this in organic synthesis, electrochemical, biotechnological and medical research. The discovery of proton sponges is the largest contribution to the theory of acids and bases in the last 50 years. The emergence of proton sponges has greatly accelerated the development of such a field of science as supramolecular chemistry.
Many new compounds and types of proton sponges have been synthesized by students, graduate students and employees of the Department of Organic Chemistry. Thus, a post-graduate student Andrey Marchenko, under the guidance of Professor Valery Ozeryanskiy, synthesized a group of substances with the shortest NH… N hydrogen bonds. By the end of 2020, the research is planned to be published in one of the international journals.
Recently, Professor Alexander Pozharsky, together with his former graduate students Alexander Antonov and Vladimir Mikshiev (now employees of St. Petersburg State University), published an article in ChemPhysChem in the journal ChemPhysChem, in which, using numerous examples, the possibility of the amide group O = C-NH2 to form a hydrogen bond due to the nitrogen atom rather than carbonyl oxygen (Fig. 2). This work is important for understanding the non-standard behavior of protein molecules.
In three other articles - "The neutral nitrogen atom of pyrrole as a π- and mixed n, π-donor in a hydrogen bond", "Modeling biologically important NH ... π interactions using peri-disubstituted naphthalenes" and "Nucleophilic substitution of a hydrogen atom in the initially inactivated pyrrole ring ”- on a related topic, published in 2019 and 2020. in leading journals J. Org. Chem. and Org. Letters, using original examples, other, little-studied types of helical stabilization of proteins, their energetics and structural specificity are considered.
Over the past 20 years, the Department of Organic Chemistry of the Faculty of Chemistry of the Southern Federal University in the group of Professor Alexander Pozharsky has been successfully working in this direction.
These studies were carried out within the framework of three RFBR grants No. 17-03-00035, 18-73-00020, 20-03-00112. Theoretical calculations were carried out by the professor of the University of Wroclaw A. Filarovsky. X-ray structural studies were carried out in the research park of St. Petersburg University, and spectral studies at the Faculty of Chemistry of the Southern Federal University and the Research Institute of Physical Chemistry.
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