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. Preliminary results strongly suggest that we have discovered the true mechanism of this transformation, which does not correspond to the schemes proposed in the scientific literature.

 

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.

NamePositionContacts
Mikhail Baranov, Ph.D.depart. dir.baranovmikes@gmail.com+7(916)3741926
Nadezhda Baleevaj. r. f.Dyuha-89@yandex.ru
Alexander Smirnovj. r. f.
Snezhana Zaytsevastud.

Selected publications

  1. Rogozhin E, Ryazantsev D, Smirnov A, Zavriev S (2018). Primary Structure Analysis of Antifungal Peptides from Cultivated and Wild Cereals. Plants (Basel) 7 (3),
  2. Zaitseva SO, Golodukhina SV, Baleeva NS, Levina EA, Smirnov AY, Zagudaylova MB, Baranov MS (2018). Azidoacetic Acid Amides in the Synthesis of Substituted Arylidene-1-H-imidazol-5-(4H)-ones. ChemistrySelect 3 (30), 8593–8596
  3. Stakheev AA, Ryazantsev DY, Zvezdina YK, Baranov MS, Zavriev SK (2018). A Novel Fluorescent GFP Chromophore Analog-Based Dye for Quantitative PCR. Biochemistry (Mosc) 83 (7), 855–860
  4. Karsakova IV, Smirnov AY, Baranov MS (2018). An effective method for the synthesis of 1,5-disubstituted 4-halo-1H-1,2,3-triazoles from magnesium acetylides. Chem Heterocycl Compd (N Y) 54 (7), 755–757
  5. Baleeva NS, Gorbachev DA, Baranov MS (2018). The Role of C2-Substituents in the Imidazolone Ring in the Degradation of GFP Chromophore Derivatives. Russ. J. Bioorganic Chem. 44 (3), 354–357
  6. Ermakova YG, Sen T, Bogdanova YA, Smirnov AY, Baleeva NS, Krylov AI, Baranov MS (2018). Pyridinium Analogues of Green Fluorescent Protein Chromophore: Fluorogenic Dyes with Large Solvent-Dependent Stokes Shift. J Phys Chem Lett 9 (8), 1958–1963
  7. Smirnov AY, Baleeva NS, Zaitseva SO, Mineev KS, Baranov MS (2018). Derivatives of Azidocinnamic Acid in the Synthesis of 2-Amino-4-Arylidene-1H-Imidazol-5(4H)-Ones. Chem Heterocycl Compd (N Y) 54 (6), 625–629
  8. Rogozhin EA, Smirnov AN (2018). Antibiotic Potential of Defense Peptides Derived from the Seeds of a Wild Grass - Barnyard Grass (Echinochloa crusgalli L.). Antibiot Med Biotekhnol 63 (34), 8–11
  9. Стахеев АА, Рязанцев ДЮ, Звездина ЮК, Баранов МС, Завриев СК (2018). Новая метка для количественной ПЦР на основе синтетического аналога хромофора зелёного флуоресцентного белка. 87 (7), 1089–1095
  10. Chen C, Liu W, Baranov MS, Baleeva NS, Yampolsky IV, Zhu L, Wang Y, Shamir A, Solntsev KM, Fang C (2017). Unveiling Structural Motions of a Highly Fluorescent Superphotoacid by Locking and Fluorinating the GFP Chromophore in Solution. J Phys Chem Lett 8 (23), 5921–5928
  11. Baleeva NS, Zaitseva SO, Gorbachev DA, Smirnov AY, Zagudaylova MB, Baranov MS (2017). The Role of N-Substituents in Radiationless Deactivation of Aminated Derivatives of a Locked GFP Chromophore. European J Org Chem 2017 (35), 5219–5224
  12. Baleeva NS, Baranov MS (2017). The Sonogashira reaction as a new method for the modification of borated analogues of the green fluorescence protein chromophore. Russ. J. Bioorganic Chem. 43 (5), 612–615
  13. Baleeva NS, Levina EA, Baranov MS (2017). Synthesis of 2-arylidene-6,7-dihydroimidazo[1,2-a]pyrazine-3,8(2H,5H)-diones by oxidation of 4-arylidene-2-methyl-1H-imidazol-5(4H)-ones with selenium dioxide. Chem Heterocycl Compd (N Y) 53 (8), 930–933
  14. Bozhanova NG, Baranov MS, Sarkisyan KS, Gritcenko R, Mineev KS, Golodukhina SV, Baleeva NS, Lukyanov KA, Mishin AS (2017). Yellow and Orange Fluorescent Proteins with Tryptophan-based Chromophores. ACS Chem Biol 12 (7), 1867–1873
  15. Vasilchenko AS, Smirnov AN, Zavriev SK, Grishin EV, Vasilchenko AV, Rogozhin EA (2017). Novel Thionins from Black Seed (Nigella sativa L.) Demonstrate Antimicrobial Activity. Int J Pept Res Ther 23 (2), 171–180
  16. Kaskova ZM, Dörr FA, Petushkov VN, Purtov KV, Tsarkova AS, Rodionova NS, Mineev KS, Guglya EB, Kotlobay A, Baleeva NS, Baranov MS, Arseniev AS, Gitelson JI, Lukyanov S, Suzuki Y, Kanie S, Pinto E, Mascio PD, Waldenmaier HE, Pereira TA, Carvalho RP, Oliveira AG, Oba Y, Bastos EL, Stevani CV, Yampolsky IV (2017). Mechanism and color modulation of fungal bioluminescence. Sci Adv 3 (4), e1602847
  17. Baranov MS, Kaskova ZM, Gritсenko R, Postikova SG, Ivashkin PE, Kislukhin AA, Moskvin DI, Mineev KS, Arseniev AS, Labas YA, Yampolsky IV (2017). Synthesis of Panal Terpenoid Core. Synlett 28 (5), 583–588
  18. Povarova NV, Markina NM, Baranov MS, Barinov NA, Klinov DV, Kozhemyako VB, Lukyanov KA (2017). A water-soluble precursor for efficient silica polymerization by silicateins. Biochem Biophys Res Commun 495 (2), 2066–2070
  19. Bozhanova NG, Baranov MS, Klementieva NV, Sarkisyan KS, Gavrikov AS, Yampolsky IV, Zagaynova EV, Lukyanov SA, Lukyanov KA, Mishin AS (2017). Protein labeling for live cell fluorescence microscopy with a highly photostable renewable signal. Chem Sci 8 (10), 7138–7142
  20. (патент) Ямпольский ИВ, Петушков ВН, Пуртов КВ, Родионова НС, Баранов МС (2016). Метод и реактивы для детекции активности люциферазы. №2596398 (изобретение)
  21. Baleeva NS, Baranov MS (2016). Synthesis and properties of 5-methylidene-3,5-dihydro-4H-imidazol-4-ones (microreview). Chem Heterocycl Compd (N Y) 52 (7), 444–446
  22. Baleeva NS, Yampolsky IV, Baranov MS (2016). Conformationally locked GFP chromophore derivatives as potential fluorescent sensors. Russ. J. Bioorganic Chem. 42 (4), 453–456
  23. Sarkisyan KS, Bolotin DA, Meer MV, Usmanova DR, Mishin AS, Sharonov GV, Ivankov DN, Bozhanova NG, Baranov MS, Soylemez O, Bogatyreva NS, Vlasov PK, Egorov ES, Logacheva MD, Kondrashov AS, Chudakov DM, Putintseva EV, Mamedov IZ, Tawfik DS, Lukyanov KA, Kondrashov FA (2016). Local fitness landscape of the green fluorescent protein. Nature 533 (7603), 397–401
  24. Tsarkova AS, Dubinnyi MA, Baranov MS, Oguienko AD, Yampolsky IV (2016). Nambiscalarane, a novel sesterterpenoid comprising a furan ring, and other secondary metabolites from bioluminescent fungus Neonothopanus nambi. MENDELEEV COMMUN 26 (3), 191–192
  25. Povarova NV, Bozhanova NG, Sarkisyan KS, Gritcenko R, Baranov MS, Yampolsky IV, Lukyanov KA, Mishin AS (2016). Docking-guided identification of protein hosts for GFP chromophore-like ligands. J Mater Chem C Mater Opt Electron Devices 4 (14), 3036–3040
  26. Olsen S, Baranov MS, Baleeva NS, Antonova MM, Johnson KA, Solntsev KM (2016). PH-Sensitive fluorophores from locked GFP chromophores by a non-alternant analogue of the photochemical: Meta effect. Phys Chem Chem Phys 18 (38), 26703–26711
  27. Балеева НС, Ямпольский ИВ, Баранов МС (2016). Борированные производные хромофора зеленого флуоресцентного белка как потенциальные флуоресцентные сенсоры. 42 (4), 501–504
  28. Baleeva NS, Tsarkova AS, Baranov MS (2016). Conformationally locked chromophores of CFP and Sirius protein. Tetrahedron Lett 57 (2728), 3043–3045
  29. Baleeva NS, Myannik KA, Yampolsky IV, Baranov MS (2015). Bioinspired Fluorescent Dyes Based on a Conformationally Locked Chromophore of the Fluorescent Protein Kaede. European J Org Chem 2015 (26), 5716–5721
  30. Rogozhin EA, Slezina MP, Slavokhotova AA, Istomina EA, Korostyleva TV, Smirnov AN, Grishin EV, Egorov TA, Odintsova TI (2015). A novel antifungal peptide from leaves of the weed Stellaria media L. B SOC CHIM BIOL 116 (0), 125–132
  31. Purtov KV, Petushkov VN, Baranov MS, Mineev KS, Rodionova NS, Kaskova ZM, Tsarkova AS, Petunin AI, Bondar VS, Rodicheva EK, Medvedeva SE, Oba Y, Oba Y, Arseniev AS, Lukyanov S, Gitelson JI, Yampolsky IV (2015). The Chemical Basis of Fungal Bioluminescence. Angew Chem Int Ed Engl 54 (28), 8124–8128
  32. Yampolsky IV, Lukyanov KA, Baranov MS (2015). Boron-containing 5-arylidene-3,5-dihydro-4H-imidazol-4-ones. 9 (133), 220
  33. Dubinnyi MA, Kaskova ZM, Rodionova NS, Baranov MS, Gorokhovatsky AY, Kotlobay A, Solntsev KM, Tsarkova AS, Petushkov VN, Yampolsky IV (2015). Novel Mechanism of Bioluminescence: Oxidative Decarboxylation of a Moiety Adjacent to the Light Emitter of Fridericia Luciferin. Angew Chem Int Ed Engl 54 (24), 7065–7067
  34. Povarova NV, Baranov MS, Kovalchuk SN, Semiletova IV, Lukyanov KA, Kozhemyako VB (2015). A novel water-soluble substrate for silicateins. Russ. J. Bioorganic Chem. 41 (3), 338–339
  35. Tsarkova AS, Dubinnyi MA, Baranov MS, Petushkov VN, Rodionova NS, Zagudaylova MB, Yampolsky IV (2015). Total synthesis of AsLn2 - A luciferin analogue from the Siberian bioluminescent earthworm Fridericia heliota. MENDELEEV COMMUN 25 (2), 99–100
  36. Dubinnyi MA, Tsarkova AS, Petushkov VN, Kaskova ZM, Rodionova NS, Kovalchuk SI, Ziganshin RH, Baranov MS, Mineev KS, Yampolsky IV (2014). Novel peptide chemistry in terrestrial animals: Natural luciferin analogues from the bioluminescent earthworm fridericia heliota. Chemistry 21 (10), 3942–3947
  37. Baranov MS, Solntsev KM, Baleeva NS, Mishin AS, Lukyanov SA, Lukyanov KA, Yampolsky IV (2014). Red-Shifted Fluorescent Aminated Derivatives of a Conformationally Locked GFP Chromophore. Chemistry 20 (41), 13234–13241
  38. Baranov MS, Fedyakina IT, Shchelkanov MY, Yampolsky IV (2014). Ring-expanding rearrangement of 2-acyl-5-arylidene-3,5-dihydro-4H-imidazol- 4-ones in synthesis of flutimide analogs. Tetrahedron 70 (23), 3714–3719
  39. Petushkov VN, Dubinnyi MA, Tsarkova AS, Rodionova NS, Baranov MS, Kublitski VS, Shimomura O, Yampolsky IV (2014). A novel type of luciferin from the siberian luminous earthworm fridericia heliota: Structure elucidation by spectral studies and total synthesis. Angew Chem Int Ed Engl 53 (22), 5566–5568
  40. Oshchepkova YI, Veshkurova ON, Salikhov SI, Zaitsev DV, Smirnov AN, Egorov TA, Rogozhin EA (2013). Comparative analysis of extracts of nigella sativa exhibiting antifungal activity against the oomycete phytophthora infestans. CHEM NAT COMPD 49 (5), 985–987
  41. Frizler M, Yampolsky IV, Baranov MS, Stirnberg M, Gütschow M (2013). Chemical introduction of the green fluorescence: Imaging of cysteine cathepsins by an irreversibly locked GFP fluorophore. Org Biomol Chem 11 (35), 5913–5921
  42. Baranov MS, Lukyanov KA, Ivashkin PE, Yampolsky IV (2013). Efficient synthetic approach to fluorescent oxazole-4-carboxylate derivatives. Synth Commun 43 (17), 2337–2342
  43. Baranov MS, Solntsev KM, Lukyanov KA, Yampolsky IV (2013). A synthetic approach to GFP chromophore analogs from 3-azidocinnamates. Role of methyl rotors in chromophore photophysics. Chem Commun (Camb) 49 (51), 5778–5780
  44. Baranov MS, Lukyanov KA, Yampolsky IV (2013). Synthesis of the chromophores of fluorescent proteins and their analogs. Russ. J. Bioorganic Chem. 39 (3), 223–244
  45. Baranov MS, Yampolsky IV (2013). Novel condensations of nitroacetic esters with aromatic aldehydes leading to 5-hydroxy-1,2-oxazin-6-ones. Tetrahedron Lett 54 (7), 628–629
  46. Baranov MS, Lukyanov KA, Borissova AO, Shamir J, Kosenkov D, Slipchenko LV, Tolbert LM, Yampolsky IV, Solntsev KM (2012). Conformationally locked chromophores as models of excited-state proton transfer in fluorescent proteins. J Am Chem Soc 134 (13), 6025–6032
  47. Leonova EI, Baranov MV, Galzitskaya OV (2012). Formation of RNA spatial structures. Mol Biol 46 (1), 34–46
  48. Baranov MS, Yampolsky IV (2012). Unusual transformations of anthranilic acid imidazolides. Chem Heterocycl Compd (N Y) 48 (7), 1108–1110
  49. Odintsova TI, Rogozhin EA, Sklyar IV, Musolyamov AK, Kudryavtsev AM, Pukhalsky VA, Smirnov AN, Grishin EV, Egorov TA (2010). Antifungal activity of storage 2S albumins from seeds of the invasive weed dandelion Taraxacum officinale Wigg. Protein Pept Lett 17 (4), 522–529
  50. Rogozhin EA, Odintsova TI, Musolyamov AK, Smirnov AN, Babakov AV, Egorov TA, Grishin EV (2009). The purification and characterization of a novel lipid transfer protein from caryopsis of barnyard grass (Echinochloa crusgalli). APPL BIOCHEM MICRO+ 45 (4), 363–368
  51. Oshchepkova YI, Veshkurova ON, Rogozhin EA, Musolyamov AK, Smirnov AN, Odintsova TI, Egorov TA, Grishin EV, Salikhov SI (2009). Isolation of the lipid-transporting protein Ns-LTP1 from seeds of the garden fennel flower (Nigella sativa). Russ. J. Bioorganic Chem. 35 (3), 315–319
  52. Urmantseva VV, Gaevskaya OA, Smirnov AV, Gukasova EA, Bairamashvili DI (2000). Specific features of a Thalictrum minus cell culture as a source of alkaloids. Russ J Plant Physiol 47 (1), 58–64
  53. Smirnov AV, Gukasova EA, Bezrukov MV, Yureva EA (1999). Chromatographic properties of Gefil, novel hydrophilic dextran gels. J ANAL CHEM+ 54 (7), 629–632

Mikhail Baranov