Igor Komarov




Igor Komarov

POSITION
Head of Supramolecular Chemistry Chair, Professor

WORK EXPERIENCE
1991–1995
Engineer
Taras Shevchenko National University of Kyiv, Kyiv (Ukraine)

1991–Present
Team leader, Scientific advisor
Enamine Ltd., Kyiv (Ukraine)

1991–2003
Lecturer
Taras Shevchenko national University of Kyiv, Kyiv (Ukraine)

2003–2007
Professor
Taras Shevchenko national University of Kyiv, Kyiv (Ukraine)

2007–2009
Head of Organic Chemistry Chair
Taras Shevchenko national University of Kyiv, Kyiv (Ukraine)

2009–Present
Vice-Director, Head of Supramolecular Chemistry Chair
Taras Shevchenko national University of Kyiv, Kyiv (Ukraine)

EDUCATION AND TRAINING


1971-1981
High School


1981-1985
Master Degree
Taras Shevchenko National University of Kyiv, Kyiv (Ukraine)

1994-1995
Postdoc at the University of Cambridge
University of Cambridge (UK), Chemistry Department (Prof. A.J. Kirby)

2000-2001
Alexander von Humboldt Research Fellowship
Institute of study of catalysis, Rostock (Germany), (Prof. Armin Börner)

RESEARCH AWARDS
February 2015
Georg Forster Research Award Alexander von Humboldt Foundation, Germany

May 2016
Merited Figure of Science and Technology of Ukraine The State Award of the Ukraine

Non-natural amino acids and peptidomimetics

Research Fields:
Chemistry

Location:
Institute of High Technology

Previous and Current Research

Previous Research

  • Synthesis of model compounds designed to study phenomena (one of the example studied was reverse anomeric effect), explore other compounds which are too complex to study or unstable (for example, enzymes or reactive intermediates, transition states), verify hypotheses and theoretical predictions (for example, mechanisms of organic reactions or catalytic transformations). This work was done in collaboration with Cambridge University, UK.
    Organic synthesis is in this case an instrument of exploration used to get new knowledge about the object of study. One of the numerous model compounds synthesized is 1-azaadamantan-2-one, a model of the cis-trans amide isomerization transition state, where the amide bond is ultimately twisted:

  • Design and synthesis of chiral bis- and monophosphine ligands for Rh-based catalysts of asymmetric homogenous hydrogenation. The work was sponsored by Alexander von Humboldt Foundation and carried out in Rostock, Institute of Study of Catalysis, Germany.
A monophospholane ligand obtained fr om tartaric acid now belongs to the best-in-class examples of the compounds giving most selective hydrogenation catalysts:
One of the ligands prepared was a camphor-derived ligand RocKyPhos, which was named after Rostock and Kyiv – the cities where the ligand had been designed and synthesized:


  • Conformationally restricted building blocks for drug design. The major sponsor of this work is a Ukrainian company Enamine.

Building blocks are reactive functionalized molecules from which drug candidates could be constructed. They are carefully selected for the use in modular synthesis of novel drug candidates, in particular, by combinatorial chemistry, parallel synthesis, or in order to realize the ideas of virtual screening. To be practically useful for the modular drug or drug candidate assembly, the building blocks should be either mono-functionalized or possess selectively addressed functional groups, for example, orthogonally protected. The restriction of conformational mobility of the building blocks molecules might enhance the efficiency and selectivity of the drugs built with their use.

Below, typical examples of building blocks are shown:


  • Direct phosphorylation of heterocyclic compounds by P(V) acid chlorides. This reaction was discovered and studied in order to obtain heterocyclic-containing phosphonic and phosphinic acids for practical applications, for example, haptens to rise catalytic antibodies or silica-immobilized Uranium extracting ligands:

  • Dynamic protection of organic functional groups by lanthanide tris-beta-diketonates. Formation of labile adducts of the lanthanide complexes with multifunctional molecules can be used for selective protection of those functional groups which react preferentially with the lanthanide complexes. This method of organic group protection does not include isolation of the protected compounds. Desired selective transformations (hydrogenation, alkylation, oxidation etc.) can be carried out just in the presence of the lanthanide tris-beta-diketonates:


Current research:

  • Peptidomimetics with photocontrolled biological activity. This work is being carried out under a Horizon 2020 Project Nr. 690973 — PELICO — H2020-MSCA-RISE-2015/H2020-MSCA-RISE-2015. Coordinator: a Ukrainian company Enamine. Beneficiaries: Cambridge University, UK; Karlsruhe Institute of Technology, Germany; Latvian Institute of Organic Synthesis, Latvia. The Project 16БП07-02 funded by the Ministry of Science and Education, Ukraine, is also devoted in part to design and synthesis of photocontrolled peptidomimetics.

The work is aimed at design, synthesis and application of the peptidomimetics, the biological activity of which can be controlled by light, as illustrated below for a photoswitchable antibiotic:


  • Design, synthesis and application of fluorine-containing and fluorescent amino acids as labels for study of peptides by NMR and fluorescent microscopy. The main collaboration partner is Karlsruhe Institute of Technology, Germany, wh ere the basic principles of the label applications were developed. The work is sponsored in part by the Alexander von Humboldt Foundation, Germany, and the Ministry of Science and Education, Ukraine (Project 16БП07-02).

Labeling of membrane-active peptides such as antimicrobial, cell-penetrating, or fusion peptides (illustrated below for an apha-helical peptide) allows for the study of the peptides in their quasi-native membrane-mimicking environment. The structure, alignment of the peptides in membranes, their mechanisms of biological action can be elucidated.


  • Use of silicon-based nanoparticles for delivery of light into tissues and cells. International collaboration in this area involves INSA Lyon, France, and Karlsruhe Institute of Technology, Germany.

The light of specific wavelengths delivered by fluorescent nanoparticles NP (especially equipped by cell-penetrating peptides like SAP or SAP-E) into cells and tissues can be used for imaging purposes, as well as for activation of photosensitive drugs.

 

  • Focused enumeration of chemical space. This work stems from the continuous interest of the research group to the application of algebra to solve chemical problems.

Enumeration of chemical space within the limits relevant to drug discovery, and navigation of the focused sub-spaces help in finding new drug leads in silico. Simple molecular descriptors, for example, exit vectors of functional groups on rigid scaffolds (illustrated below on a spirocyclic scaffold example) can help in statistical analysis of chemical structures, QSAR studies, scaffold hopping and other instruments on medicinal chemistry:


Methodological and Technical Expertise

  • Molecular design
  • Organic synthesis of high complexity
  • Nuclear Magnetic Resonance, in particular, of peptides and proteins
  • Pharmacokinetic and Pharmacodynamic

Selected Publications


Budnyak, T.M., Strizhak, A.V., Gładysz-Płaska, A., Sternik, D., Komarov, I.V., Kołodyńska, D., Majdan, M., Tertykh, V.T.
Silica with immobilized phosphinic acid-derivative for uranium extraction.
J. Hazard. Mater, 2016, 314 (15), 326-340, DOI: 10.1016/j.jhazmat.2016.04.056

Oleg Babii, Sergii Afonin, Liudmyla V. Garmanchuk, Viktoria V. Nikulina, Tetiana V. Nikolaienko, Olha V. Storozhuk, Dmytro V. Shelest, Olga I. Dasyukevich, Liudmyla I. Ostapchenko, Volodymyr Iurchenko, Sergey Zozulya, Anne S. Ulrich, Igor V. Komarov.
Direct Photocontrol of Peptidomimetics: An Alternative to Oxygen-Dependent Photodynamic Cancer Therapy.
Angew. Chem. Int. Ed. 2016, 55, 5493 – 5496.

Oleksandr O. Grygorenko, Pavlo Babenko, Dmitry M. Volochnyuk, Oleksii Raievskyi, Igor V. Komarov.
Following Ramachandran: exit vector plots (EVP) as a tool to navigate chemical space covered by 3D bifunctional scaffolds.
The case of cycloalkanes. RSC Adv., 2016, 6, 17595–17605.

Andriy V. Tymtsunik, Serhii O. Kokhan, Yevhen M. Ivon, Igor V. Komarov, Oleksandr O. Grygorenko.
Intramolecular functional group differentiation as a strategy for the synthesis of bridged bicyclic β-amino acids.
RSC Adv., 2016, 6, 22737–22748.

Anton V. Chernykh, Dmytro S. Radchenko, Oleksandr O. Grygorenko, Constantin G. Daniliuc, Dmitriy M. Volochnyuk, Igor V. Komarov.
Synthesis and Structural Analysis of Angular Monoprotected Diamines Based on Spiro[3.3]heptane Scaffold.
J. Org. Chem. 2015, 80, 3974−3981.

T. Serdiuk, I. Bakanovich, V. Lysenko, S. A. Alekseev, V. A. Skryshevsky, S. Afonin, E. Berger, A. Géloën I. V. Komarov.
Delivery of SiC-based nanoparticles into live cells driven by cell-penetrating peptides SAP and SAP-E.
RSC Adv. 2015, 5, 20498-20502.

Yevhen M. Ivon, Andriy V. Tymtsunik, Igor V. Komarov, Oleg V. Shishkin, Oleksandr O. Grygorenko.
Synthesis of a 2,5-Diazabicyclo[2.2.1]heptane-Derived α,β-Diamino Acid.
Synthesis, 2015, 47 (08), 1123-1130.

Aleksandr Yu. Ishchenko, Stanislav Yanik, Eduard B. Rusanov, Igor V. Komarov, Anthony J. Kirby.
An Expedient and Practical Approach to Functionalized 3-Aza-, 3-Oxa-, and 3-Thiabicyclo[3.3.1]nonane Systems.
Synthesis 2015, 47 (03), 367-376.

Igor V. Komarov, Stanislav Yanik, Aleksandr Yu. Ishchenko, John E. Davies, Jonathan M. Goodman, Anthony J. Kirby.
The Most Reactive Amide As a Transition-State Mimic For cis−trans Interconversion.
J. Am. Chem. Soc. 2015, 137, 926−930.

Dmytro Bandak, Oleg Babii, Roman Vasiuta, Igor V. Komarov, Pavel K. Mykhailiuk.
Design and Synthesis of Novel 19F-Amino Acid: A Promising 19F NMR Label for Peptide Studies.
Org. Lett. 2015, 17 (2), 226–229.

Olexiy S. Artamonov, Evgeniy Y. Slobodyanyuk, Dmitriy M. Volochnyuk, Igor V. Komarov, Andrey A. Tolmachev, Pavel K. Mykhailiuk.
Synthesis of Trifluoromethyl-Substituted 3-Azabicyclo[n.1.0]alkanes: Advanced Building Blocks for Drug Discovery.
Eur. J. Org. Chem. 2014, 3592–3599.

Anton N. Tkachenko, Pavel K. Mykhailiuk, Dmytro S. Radchenko, Oleg Babii, Sergii Afonin, Anne S. Ulrich, and Igor V. Komarov.
Design and Synthesis of a Monofluoro-Substituted Aromatic Amino Acid as a Conformationally Restricted 19F NMR Label for Membrane-Bound Peptides.
Eur. J. Org. Chem. 2014, 3584–3591.

Andriy V. Tymtsunik, Yevhen M. Ivon, Igor V. Komarov, Oleksandr O. Grygorenko.
Synthesis of Boc-protected 4,5-methano--proline.
Tetrahedron Letters 2014, 55, 3312–3315.

Oleg Babii, Sergii Afonin, Marina Berditsch, Sabine Reiβer, Pavel K. Mykhailiuk, Vladimir S. Kubyshkin, Thomas Steinbrecher, Anne S. Ulrich, Igor V. Komarov.
Controlling Biological Activity with Light: Diarylethene-Containing Cyclic Peptidomimetics.
Angew. Chem. Int. Ed. 2014, 53, 3392 –3395.

Anton V. Chernykh, Dmytro S. Radchenko, Oleksandr O. Grygorenko, Dmitriy M. Volochnyuk, Svitlana V. Shishkina, Oleg V. Shishkin, Igor V. Komarov.
Conformationally restricted glutamic acid analogues: stereoisomers of 1-aminospiro[3.3]-heptane-1,6-dicarboxylic acid.
RSC Adv. 2014, 4, 10894-10902.

Andriy V. Tymtsunik, Vitaliy A. Bilenko, Oleksandr O. Grygorenko, Igor V. Komarov.
Gram-Scale Synthesis of 3,5-Methanonipecotic Acid, a Nonchiral Bicyclic -Amino Acid.
Synlett 2014, 25, 0355-0358.

Anton N. Tkachenko, Dmytro S. Radchenko, Pavel K. Mykhailiuk, Sergii Afonin, Anne S. Ulrich, and Igor V. Komarov.
Design, Synthesis, and Application of a Trifluoromethylated Phenylalanine Analogue as a Label to Study Peptides by Solid-State 19F NMR Spectroscopy.
Angew. Chem. Int. Ed. 2013, 52, 6504–6507.

Dmytro S. Radchenko, Oleg M. Michurin, Oleksandr O. Grygorenko, Kathi Scheinpflug, Margitta Dathe, Igor V. Komarov.
Confining the  space of basic natural amino acids: cyclobutane-derived χ1,χ2-constrained analogues of arginine, lysine and ornithine.
Tetrahedron 2013, 69, 505-511.

Vladimir S. Yarmolchuk, Oleg V. Shishkin, Viktoriia S. Starova, Olga A. Zaporozhets, Olga Kravchuk, Sergey Zozulya, Igor V. Komarov, Pavel K. Mykhailiuk.
Synthesis and Characterization of β-Trifluoromethyl-Substituted Pyrrolidines.
Eur. J. Org. Chem. 2013, 3086–3093.

Olexiy S. Artamonov, Evgeniy Y. Slobodyanyuk, Oleg V. Shishkin, Igor V. Komarov, Pavel K. Mykhailiuk.
Synthesis of isomeric 6-trifluoromethyl-3-azabicyclo[3.1.0]hexanes: conformationally restricted analogues of 4-trifluoromethylpiperidine.
Synthesis, 2013, 45, 225-230.

Anton N. Tkachenko, Pavel K. Mykhailiuk, Sergii Afonin, Dmytro S. Radchenko, Vladimir S. Kubyshkin, Anne S. Ulrich, Igor V. Komarov.
A 19F NMR Label To Substitute Polar Amino Acids in Peptides: A CF3-Substituted Analogue of Serine and Threonine.
Angew. Chem. Int. Ed. 2013, 52, 1486 –1489.

Vladimir S. Kubyshkin, Pavel K. Mykhailiuk, Sergii Afonin, Anne S. Ulrich, Igor V. Komarov.
Incorporation of cis- and trans-4,5-Difluoromethanoprolines into Polypeptides.
Org. Lett., 2012, 14 (20), 5254–5257.

Oleksandr O. Grygorenko, Roman Prytulyak, Dmitriy M. Volochnyuk, Volodymyr Kudrya, Oleksiy V. Khavryuchenko, Igor V. Komarov.
Focused enumeration and assessing the structural diversity of scaffold libraries: conformationally restricted bicyclic secondary diamines.
Mol. Divers. 2012, 16 (3), 477-487.

Andriy V. Tymtsunik, Vitaliy A. Bilenko, Yevhen M. Ivon, Oleksandr O. Grygorenko, Igor V. Komarov.
Synthesis of a novel Boc-protected cyclopropane-modified proline analogue.
Tetrahedron Letters 2012, 53, 3847–3849.

Vladimir S. Yarmolchuk, Ivan L. Mukan, Oleksandr O. Grygorenko, Andrey A. Tolmachev, Svitlana V. Shishkina, Oleg V. Shishkin, and Igor V.
Komarov An Entry into Hexahydro-2H-thieno[2,3-c]pyrrole 1,1-Dioxide Derivatives.
J. Org. Chem., 2011, 76 (17), pp 7010–7016.

Oleksandr O. Grygorenko, Dmytro S. Radchenko, Dmitriy M. Volochnyuk, Andrey A. Tolmachev, and Igor V. Komarov.
Bicyclic Conformationally Restricted Diamines.
Chem. Rev., 2011, 111 (9), pp 5506–5568

Dmytro S. Radchenko, Sergiy O. Pavlenko, Oleksandr O. Grygorenko, Dmitriy M. Volochnyuk, Svitlana V. Shishkina, Oleg V. Shishkin, Igor V. Komarov.
Cyclobutane-Derived Diamines: Synthesis and Molecular Structure.
J. Org. Chem. 2010, 75, 5941–5952.

Dmytro S. Radchenko, Nataliya Kopylova, Oleksandr O. Grygorenko, Igor V. Komarov.
Conformationally Restricted Nonchiral Pipecolic Acid Analogues.
J. Org. Chem. 2009, 74, 5541-5544.

Anton N. Tkachenko, Dmytro S. Radchenko, Pavel K. Mykhailiuk, Oleksandr O. Grygorenko, and Igor V. Komarov.
4-Fluoro-2,4-methanoproline.
Org. Lett. 2009, 11, No. 24, 5674-5676.

Pavel K. Mykhailiuk, Sergii Afonin, Gennady V. Palamarchuk, Oleg V. Shishkin, Anne S. Ulrich, Igor V. Komarov.
Synthesis of Trifluoromethyl-Substituted Proline Analogues as 19F NMR Labels for Peptides in the Polyproline II Conformation.
Angew. Chem. Int. Ed. 2008, 47, 5765 –5767.

Pavel K. Mikhailiuk, Sergii Afonin, Alexander N. Chernega, Eduard B. Rusanov, Maxim O. Platonov, Galina G. Dubinina, Marina Berditsch, Anne S. Ulrich, Igor V. Komarov.
Conformationally rigid trifluoromethyl-substituted -amino acid designed for peptide structure analysis by solid-state 19F NMR spectroscopy.
Ed. Engl., 2006, vol. 45, p. 5659-5661.

Komarov I. V., Davies J. E., Kirby A. J.
Structural correlations for nucleophilic addition to the C=O group: the solvation angle.
Helv. Chim. Acta, 2003, vol. 86, p. 1222-1233.

Komarov I. V., Monsees A., Spannenberg A., Baumann W., Schmidt U., Fischer C., Börner A.
Chiral oxo- and oxy-functionalised diphosphane ligands derived from camphor for rhodium(I)-catalysed enantioselective hydrogenation.
Eur. J. Org. Chem., 2003, No 1, p. 138-150.

Komarov I. V., Monsees A., Kadyrov R., Fischer C., Schmidt U., Börner A.
A new hydroxydiphosphine as a ligand for Rh(I)-catalysed enantioselective hydrogenation.
Tetrahedron: Asymmetry, 2002, vol. 13, No 15, p. 1615-1620.

Komarov I. V., Bilenko V. A., Davies J. E., Rawson J. Kirby A. J. M.
Structure and chemistry of a zwitterionic amine-aldehyde adduct.
Chem. Commun., 2002, No 18, p. 2106-2107.

Komarov I. V., Feeder N. Kirby A.. J.
Synthesis, structure and reactions of the most twisted amide.
J. Chem. Soc., Perkin Trans. 2., 2001, p. 522-529.

Komarov I. V.
Organic Molecules with Abnormal Geometric Parameters.
Russian Chemical Reviews, 2001, vol. 70, No 12, p. 991-1016.

Igor V. Komarov, Aleksandr V. Strizhak, Mikhail Yu.Kornilov, Aleksandr N. Kostyuk, Andrey A. Tolmachev.
Direct Phosphorylation of N-Protected Imidazoles and Benzoimidazoles-A Route to 1H-Imidazol(benzoimidazol)-2-yl Phosphonic and Phosphinic Acids and Their Derivatives.
Synth. Commun. 1998, 28 ( 13), 2355-2370.

Anthony J. Kirby, Igor V. Komarov, Peter D.Wothers, Neil Feeder.
The Most Twisted Amide: Structure and Reactions.
Angew. Chem. Int. Ed. 1998, 37, No. 6, p. 785-786.

Komarov I. V., Denisenko V.E., Kornilov M.Yu.
Selective catalytic hydrogenation in the presence of lanthanide tris--diketonates as "protecting" reagents.
Tetrahedron. -1994. -Vol. 50. -N 23. -P. 6921-6926.

Komarov I. V., Denisenko V.E., Kornilov M.Yu.
A new approach to the selective alkylation of difunctional compounds.
Tetrahedron. -1993. -Vol. 49. -N 34. -P. 7593-7598.

Contacts


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