Group of chemistry of heterocyclic compounds

The main direction of the group's research is the development of new approaches to the synthesis of heterocyclic compounds, as well as the application of these approaches in the synthesis of substances which have biological activity or are models in the study of biological processes.

The main activity of the group is aimed at the development of new and improvement of old approaches to the synthesis of heterocyclic compounds, as well as the applied use of the methods obtained in the synthesis of the target compounds. The next ones act in the capacity of the target compounds:

  • Model compounds which simulate chromophores of fluorescent proteins
  • New fluorescent dyes
  • New fluorogenic dyes
  • Other biologically active compounds


One of the main directions of our research is the study of the structure of stained and fluorescent proteins chromophores. Counter-synthesis is certainly the key tool of such studies. Earlier this approach allowed to confirm the structure of chromophores of proteins asFP595, Kaede and zFP538, as well as to understand the mechanism of dsRed protein chromophore formation.

Currently, within the framework of project 16-33-60116-mol-a-dk ("Study of the chromophores of fluorescent proteins: from structural and functional studies to the search for new fluorophores for living systems"), we also confirmed the structure of the chromophores of yellow and orange proteins, which contain the residue tryptophan, and also work on the synthesis of a model compound, which simulate the chromophore structure of the laRFP protein was started.

Study of a new class of fluorescent dyes based on the borated chromophore GFP

Another interesting result of our studies was the detection of the dependence of the quantum yield of fluorescence of chromophores on their mobility, which helped us synthesize a number of high fluorescence derivatives of the GFP chromophore by means of coordination fixation with a boron atom, which ones can be reliably attributed to a new separate group of fluorescent markers called BOBDI BOronBenzyliDeneImidazolone). This discovery made it possible in practice to demonstrate the possibility of using such compounds as fluorescent labels for living systems (the work was realized within the framework of the RFBR project 14-03-31162 mol_a, "A new class of fluorescent dyes for biology").


Existing fluorescent dyes used for staining living systems have a number of significant disadvantages and are unsuitable for solving a certain range of problems (for example, there are practically no compounds with Stokes shifts of more than 100 nm among them). At the same time, the chromophores of fluorescent proteins do not have many of the disadvantages inherent in the existing dyes, and therefore they are an excellent basis for creating new dyes.

Development of new fluorogenic dyes, including ones based on the chromophores of fluorescent proteins

One of the new and modern methods of fluorescent labeling of biological cells is the use of so-called fluorogenic dyes – substances, which do not have a pronounced fluorescence in a free form and acquire it only when bound to the target object.

One of the promising candidates for the role of such substances are the chromophores of fluorescent proteins and their derivatives.

In this regard, in our group, the creation and study of various fluorogenic compounds is actively conducted.

Development of new approaches to the synetze of heterocyclic compounds

Our team has long been studying the chemistry of chromophores of fluorescent proteins based on the molecule - 4-benzylidene-imidazole-5-ones. During this work we have created several new approaches to the synthesis of these compounds, and in parallel many unexpected transformations associated with the use of esters of nitroacetic and azidoacetic acids were discovered.

In particular, the method of synthesis of 5-hydroxy-1,2-oxazine-6-ones discovered by us allows us to take a new look at one of the methods for the synthesis of isoxazole-3,5-dicarboxylic acid derivatives, the Dornow reaction.



Similarly, the transformations of the derivatives of azidoacetic acid and their phosphazenes observed by us are also not reflected in the scientific literature, which suggests the possibility of creating new ways of synthesizing heterocyclic systems and from these reagents.

All publications (show selected)


Mikhail Baranov

Shиненный с G-квадруплексами, увеличивает флуоресценцию синтетических аналогов хромофора GFPort Duplex Module Coupled to G-Quadruplexes Increases Fluorescence of Synthetic GFP Chromophore Analogues

In collaboration with The group of molecular tools for living system studies

Aptasensors became popular instruments in bioanalytical chemistry and molecular biology. To increase specificity, perspective signaling elements in aptasensors can be separated into a G-quadruplex (G4) part and a free fluorescent dye that lights up upon binding to the G4 part. However, current systems are limited by relatively low enhancement of fluorescence upon dye binding. Here, we added duplex modules to G4 structures, which supposedly cause the formation of a dye-binding cavity between two modules. Screening of multiple synthetic GFP chromophore analogues and variation of the duplex module resulted in the selection of dyes that light up after complex formation with two-module structures and their RNA analogues by up to 20 times compared to parent G4s. We demonstrated that the short duplex part in TBA25 is preferable for fluorescence light up in comparison to parent TBA15 molecule as well as TBA31 and TBA63 stabilized by longer duplexes. Duplex part of TBA25 may be partially unfolded and has reduced rigidity, which might facilitate optimal dye positioning in the joint between G4 and the duplex. We demonstrated dye enhancement after binding to modified TBA, LTR-III, and Tel23a G4 structures and propose that such architecture of short duplex-G4 signaling elements will enforce the development of improved aptasensors.

New labels and approaches for low toxic fluorescent labeling of proteins in living cells

In collaboration with Group of molecular tags for optical nanoscopy

Ultraviolet, often used in fluorescence microscopy and nanoscopy, is extremely toxic to cells. Therefore, it is preferable to use labels in the green and red spectral regions.

We found the ability of the fluorescent protein mAvicFP1 to spontaneously blink under the influence of less toxic blue light, and applied this property to nanoscopy and to track single molecules of labeled proteins in living cells.

Fluorogen-activating proteins are new generation labeling systems based on transient interaction of a genetically encoded protein and  externally applied fluorogen. We have created and used  in living cells a new red fluorogen N871b for the FAST reporter protein.

A method of protein labeling in live cells based on fluorogen and fluorogen-binding protein

In collaboration with Laboratory of Chemistry of Metabolic Pathways,  Group of synthetic biology,  Laboratory of genetically encoded molecular tools

We developed a new method of target protein labeling called Protein-PAINT. This method is based on reversible binding of a protein domain with a fluorogenic dye that leads to a strong increase in fluorescence intensity. Using computer molecular docking we engineered three mutants of bacterial lipocalin Blc with different affinities to the fluorogen. It was shown that the fluorogen enters live cell quickly and stains target proteins fused with the Blc mutants. The new method ensures an order of magnitude higher photostability of the fluorescence signal in comparison with fluorescent proteins. Protein-PAINT also enables prolonged super-resolution fluorescence microscopy of living cells in both single molecule detection and stimulated emission depletion regimes.