Ivan A. Boldyrev

Education

PeriodCountry, cityEducation institutionAdditional info
1998–2004 Moscow Moscow State Academy of Fine Chemical Technology Ingineer (Biotechnology)
2004–2007 Moscow Institute of Bioorganic Chemistry postgraduate studentship

Scientific interests

syntheses of fluorescent and biologically active lipids, biophysics of model and biological membranes, lateral pressure in lipid bilayers

Selected publications

  1. Alekseeva A.S., Maslov M.A., Antipova N.V., Boldyrev I.A. (2011). Comparison of two lipid/DNA complexes of equal composition and different morphology. Colloids Surf B Biointerfaces 88 (1), 512–6 [+]

    Two types of complexes were prepared from a cationic cholesterol derivative, dioleoylphos-phatidylcholine and DNA. Depending on the preparation procedure complexes were either dense snarls of lipid covered DNA (type A) or multilayer liposomes with DNA between layers (type B). The transfection efficiency of the snarl-shaped complexes was low but positive. The transfection efficiency of the liposome-shaped complexes was zero, while DNA release upon their interaction with anionic liposomes was 1.7 times higher. The differences in transfection efficacy and DNA release could not be ascribed to the difference in resistance of complexes to decomposition upon interaction with anionic liposomes or intracellular environment since the lipid composition of complexes is the same. Instead the complexes in which lipoplex phase is more continuous (type A) should require more anionic lipids or more time within a cell for complete decomposition. Prolonged life time should lead to the higher probability of DNA expression.

  2. Konshina A.G., Boldyrev I.A., Utkin Y.N., Omelkov A.V., Efremov R.G. (2011). Snake cytotoxins bind to membranes via interactions with phosphatidylserine head groups of lipids. PLoS ONE 6 (4), e19064 [+]

    The major representatives of Elapidae snake venom, cytotoxins (CTs), share similar three-fingered fold and exert diverse range of biological activities against various cell types. CT-induced cell death starts from the membrane recognition process, whose molecular details remain unclear. It is known, however, that the presence of anionic lipids in cell membranes is one of the important factors determining CT-membrane binding. In this work, we therefore investigated specific interactions between one of the most abundant of such lipids, phosphatidylserine (PS), and CT 4 of Naja kaouthia using a combined, experimental and modeling, approach. It was shown that incorporation of PS into zwitterionic liposomes greatly increased the membrane-damaging activity of CT 4 measured by the release of the liposome-entrapped calcein fluorescent dye. The CT-induced leakage rate depends on the PS concentration with a maximum at approximately 20% PS. Interestingly, the effects observed for PS were much more pronounced than those measured for another anionic lipid, sulfatide. To delineate the potential PS binding sites on CT 4 and estimate their relative affinities, a series of computer simulations was performed for the systems containing the head group of PS and different spatial models of CT 4 in aqueous solution and in an implicit membrane. This was done using an original hybrid computational protocol implementing docking, Monte Carlo and molecular dynamics simulations. As a result, at least three putative PS-binding sites with different affinities to PS molecule were delineated. Being located in different parts of the CT molecule, these anion-binding sites can potentially facilitate and modulate the multi-step process of the toxin insertion into lipid bilayers. This feature together with the diverse binding affinities of the sites to a wide variety of anionic targets on the membrane surface appears to be functionally meaningful and may adjust CT action against different types of cells.

  3. Boldyrev I.A., Molotkovskiĭ J.G. (2010). New 4,4-Difluoro-3a,4a-Diaza-s-Indacene (BODIPY)-Labeled Sphingolipids for Membrane Studies. Russ. J. Bioorg. Chem. 36 (4), 508–511 [+]

    The synthesis of a series of new fluorescently labeled sphingolipids containing a 4,4-difluoro-
    1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene-8-yl (Me4-BODIPY-8) group at the ω-position of a
    fatty acyl residue is described. The obtained probes were used in studies of biological and model membrane
    systems.

  4. Sachl R., Boldyrev I., Johansson L.B.A. (2010). Localisation of BODIPY-labelled phosphatidylcholines in lipid bilayers. Phys. Chem. Chem. Phys. , [+]

    A series of sn-2 acyl-labelled phosphatidyl-cholines (PC), bearing 4,4-difluoro-1-3-5-7-tetra-methyl-4-bora-3a,4a-diaza-s-indacene-8-yl (Me4-BODIPY) at the end of the Cn-acyl chains were solubilised in unilamellar vesicles and studied with respect to the order and location of the Me4-BODIPY (denoted: B) group. The obtained results are based on time-resolved electronic energy transfer from donors (2-(9-anthroyloxy)-stearic acid) localised in the lipid–water interface to acceptors BnPC (n = 3, 5, 7, 9, 11, 13, 15), as well as the energy migration among the Me4-BODIPY groups of BnPC:s. The donor–acceptor and the donor–donor experiments strongly suggest that the Me4-BODIPY group in BnPC tends to loop back close to the lipid–water interface. The Me4-BODIPY groups, residing in the two bilayer leaflets, are located at approximately the same depth, and transversally separated by ca. 27 Å for all n-values. Close to the interface, the optimal transversal distribution widens somewhat with increasing length of the sn-2 acyl chain. The obtained order parameter profile of the BnPC:s is also compatible with such a location.

  5. Sugár I.P., Zhai X., Boldyrev I.A., Molotkovsky J.G., Brockman H.L., Brown R.E. (2010). Characterization of the lateral distribution of fluorescent lipid in binary-constituent lipid monolayers by principal component analysis. Int J Biomed Imaging 2010, 125850 [+]

    Lipid lateral organization in binary-constituent monolayers consisting of fluorescent and nonfluorescent lipids has been investigated by acquiring multiple emission spectra during measurement of each force-area isotherm. The emission spectra reflect BODIPY-labeled lipid surface concentration and lateral mixing with different nonfluorescent lipid species. Using principal component analysis (PCA) each spectrum could be approximated as the linear combination of only two principal vectors. One point on a plane could be associated with each spectrum, where the coordinates of the point are the coefficients of the linear combination. Points belonging to the same lipid constituents and experimental conditions form a curve on the plane, where each point belongs to a different mole fraction. The location and shape of the curve reflects the lateral organization of the fluorescent lipid mixed with a specific nonfluorescent lipid. The method provides massive data compression that preserves and emphasizes key information pertaining to lipid distribution in different lipid monolayer phases. Collectively, the capacity of PCA for handling large spectral data sets, the nanoscale resolution afforded by the fluorescence signal, and the inherent versatility of monolayers for characterization of lipid lateral interactions enable significantly enhanced resolution of lipid lateral organizational changes induced by different lipid compositions.

  6. Boldyrev I.A., Pavlova Iu.B., Molotkovskiĭ Iu.G. (2009). Synthesis and characteristics of new fluorescent probes based on cardiolipin. Bioorg. Khim. 35 (2), 239–44 [+]

    New fluorescent lipid probes, cardiolipin derivatives AV12-CL and B7-CL, bearing the residues of 12-(9-anthryl)-11E-dodecenoic and 7-(4,4-difluoro-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacen-8-yl)heptanoic acid, respectively, have been synthesized by acylation of 1-lysocardiolipin, which had been obtained from bovine heart cardiolipin by enzymatic hydrolysis with bacterial lipase. The resulting probes are intended for the study of protein-anionic phospholipid interactions.

  7. Omelkov A.V., Pavlova Iu.B., Boldyrev I.A., Molotkovskiĭ Iu.G. (2009). Depth-dependent investigation of the apolar zone of lipid membranes using a series of fluorescent probes, Me4-BODIPY-8-labeled phosphatidylcholines. Bioorg. Khim. 33 (5), 544–9 [+]

    A series of lipid probes, phosphatidylcholines labeled with Me4-BODIPY-8 (4,4-difluoro-1,3,5,7- tetramethyl-4-bora-3a,4a-diaza-s-indacen-8-yl) fluorophore attached to the end of an acyl residue at different distances from the polar head, were used as depth-dependent probes for the apolar zone of model membrane systems, large unilamellar vesicles (LUVs). Data on the anisotropy of probe fluorescence demonstrated different mobility profiles for the fluorophore microenvironment in LUVs of different composition at various temperatures, which indicates a high sensitivity of these probes as tools for studying membrane systems. An interesting anomaly was observed for LUVs from dimiristoylphosphatidylcholine (DMPC) or from a DMPC-cholesterol mixture: the anisotropy of the fluorophore located near the bilayer center is larger than that of the fluorophore located further from the center; i.e., the mobility of the microenvironment is lower in the first case. This anomaly is supposed to result from the penetration of the unlabeled long chain of the probes into the opposite bilayer leaflet. Such a possibility should be taken into account in constructing fluorescent probes and interpreting the results.

  8. Boldyrev I.A., Zhai X., Momsen M.M., Brockman H.L., Brown R.E., Molotkovsky J.G. (2007). New BODIPY lipid probes for fluorescence studies of membranes. J. Lipid Res. 48 (7), 1518–32 [+]

    Many fluorescent lipid probes tend to loop back to the membrane interface when attached to a lipid acyl chain rather than embedding deeply into the bilayer. To achieve maximum embedding of BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) fluorophore into the bilayer apolar region, a series of sn-2 acyl-labeled phosphatidylcholines was synthesized bearing 4,4-difluoro-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene-8-yl (Me(4)-BODIPY-8) at the end of C(3)-, C(5)-, C(7)-, or C(9)-acyl. A strategy was used of symmetrically dispersing the methyl groups at BODIPY ring positions 1, 3, 5, and 7 to decrease fluorophore polarity. Iodide quenching of the phosphatidylcholine probes in bilayer vesicles confirmed that the Me(4)-BODIPY-8 fluorophore was embedded in the bilayer. Parallax analysis of Me(4)-BODIPY-8 fluorescence quenching by phosphatidylcholines containing iodide at different positions along the sn-2 acyl chain indicated that the penetration depth of Me(4)-BODIPY-8 into the bilayer was determined by the length of the linking acyl chain. Evaluation using monolayers showed minimal perturbation of <10 mol% probe in fluid-phase and cholesterol-enriched phosphatidylcholine. Spectral characterization in monolayers and bilayers confirmed the retention of many features of other BODIPY derivatives (i.e., absorption and emission wavelength maxima near 498 nm and approximately 506-515 nm) but also showed the absence of the 620-630 nm peak associated with BODIPY dimer fluorescence and the presence of a 570 nm emission shoulder at high Me(4)-BODIPY-8 surface concentrations. We conclude that the new probes should have versatile utility in membrane studies, especially when precise location of the reporter group is needed.

  9. Boldyrev I.A., Molotkovskiĭ I.G. (2006). [A synthesis and properties of new 4,4-difluoro-3a,4a-diaza-s-indacene (BODIPY))-labeled lipids]. Bioorg. Khim. 32 (1), 87–92 [+]

    A series of fluorescently labeled fatty acids of various chain lengths with 4,4-difluoro-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene-8-yl (Me4-BODIPY-8) residue in the omega-position were synthesized. These acids were used to prepare new fluorescently labeled phosphatidylcholines, sphingomyelin, and galactosyl ceramide. Taking into account the symmetry of the Me4-BODIPY-8-fluorophore, one can presume that, in most bilayer membrane systems, this fluorophore is would be embedded into the bilayer.

  10. Boldyrev I.A., Molotkovskiĭ Yu.G. (2005). A synthesis of new rigid fluorescent bichromophoric probes for studying mechanisms of donor-donor energy migration. Bioorg. Khim. 31 (3), 331–4 [+]

    Three new fluorescent probes were synthesized for improving the method of studying donor-donor energy migration (DDEM). Each probe has two identical fluorescent 7-diethylaminocoumarin-3-carbonyl groups attached to a rigid bisteroid dodecacyclic spacer through additional inserts. In two probes, the inserts are beta-Ala and L-Ser residues, which provide for a different nearest environment of the fluorophores. The third probe has identical beta-Ala inserts. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2005, vol. 31, no. 3; see also http://www.maik.ru.

  11. Boldyrev I.A., Molotkovskiĭ Yu.G. (2004). Fluorescent properties of 9-anthracenecarboxamides. Bioorg. Khim. 30 (6), 649–55 [+]

    A number of new 9-anthracenecarboxamides are synthesized in order to create new fluorescent probes for studying biological systems. The parameters of their fluorescence in organic solvents of various polarities are investigated, and possible mechanisms of internal quenching of fluorescence of these compounds are discussed. One of the compounds, 4-ethoxycarbonylphenylamide of 9-anthracenecarboxylic acid, is shown to be a promising basis for the development of a new fluorescent probe. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 6; see also http://www.maik.ru.

  12. Boldyrev I.A., Grechishnikova I.V., Pavlova Iu.B., Molotkovskiĭ Iu.G. (2004). Synthesis and properties of fluorescently-labelled triglyceride, derivative of the antineoplastic agent sarcolysin. Bioorg. Khim. 30 (1), 80–3 [+]

    A new fluorescent probe, a 3-perylenoyl derivative of the lipophilized antitumor drug merphalan (sarcolysine), was synthesized. The probe is suitable for studying intracellular traffic and metabolism of merphalan and its derivatives. The perylenoyl fluorescence is partially quenched by the merphalan chromophore, which broadens the probe potentialities. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 1; see also http://www.maik.ru.