Молотковский Юлиан Георгиевич

Личная информация

Юл. Г. Молотковский ― сотрудник лаборатории химии липидов ИБХ с ее основания в 1963 г. Выпускник МИТХТ им. М. В. Ломоносова 1957 г, был в 1959 г. принят в аспирантуру Института химии природных соединений АН СССР в лабораторию химии антибиотиков (заведующий - академик М.М. Шемякин).

 

Среди работ Ю. Г. Молотковского — более 180 научных статей; Государственная премия СССР (1985 г.); он член редколлегий журналов «Биоорганическая химия» и «Биологические мембраны».

Образование

Период обученияСтрана, городУчебное заведениеДополнительная информация
Россия, Москва Институт химии природных соединений АН СССР (ИХПС) Присуждена учёная степень кандидата химических наук
1957 Россия, Москва Московский институт тонкой химической технологии имени М.В. Ломоносова (МИТХТ) Диплом химика
1985 Россия, Москва Институт биоорганической химии имени М.М. Шемякина АН СССР (ИБХ) Присуждена учёная степень доктора химических наук

Научные интересы


Премии и заслуги


Основные научные результаты

После защиты кандидатской диссертации Ю. Г. Молотковский специализировался в липидной химии и мембранологии, в этой области ему принадлежит ряд новых разработок: методы синтеза труднодоступных фосфолипидов, новый метод разделения рацемических спиртов на антиподы, синтезы флуоресцентных и фотореактивных зондов. В сотрудничестве с отечественными и зарубежными учеными обнаружены новые закономерности в липид-белковой организации липопротеинов крови, мембран эритроцитов и вируса гриппа, изучена рецепция холерного токсина ганглиозидами, топография в мембране цитохрома Р-450, проведена серия модельных исследований бислойных мембран. После защиты докторской диссертации (1985 г.) одно из важнейших направлений лаборатории химии липидов, которой Ю. Г. Молотковский руководил с 1991 по 2007 г., ― синтезы противоопухолевых препаратов липидной природы и разработка способов направленной их доставки к опухолям.

Членство в научных обществах


Гранты и проекты

ПериодДополнительная информация

Избранные публикации

  1. Alekseeva A.S., Moiseeva E.V., Onishchenko N.R., Boldyrev I.A., Singin A.S., Budko A.P., Shprakh Z.S., Molotkovsky J.G., Vodovozova E.L. (2017). Liposomal formulation of a methotrexate lipophilic prodrug: assessment in tumor cells and mouse T-cell leukemic lymphoma. Int J Nanomedicine 12, 3735–3749 [+]

    In a previous study, a formulation of methotrexate (MTX) incorporated in the lipid bilayer of 100-nm liposomes in the form of diglyceride ester (MTX-DG, lipophilic prodrug) was developed. In this study, first, the interactions of MTX-DG liposomes with various human and mouse tumor cell lines were studied using fluorescence techniques. The liposomes composed of egg phosphatidylcholine (PC)/yeast phosphatidylinositol/MTX-DG, 8:1:1 by mol, were labeled with fluorescent analogs of PC and MTX-DG. Carcinoma cells accumulated 5 times more MTX-DG liposomes than the empty liposomes. Studies on inhibitors of liposome uptake and processing by cells demonstrated that the formulation used multiple mechanisms to deliver the prodrug inside the cell. According to the data from the present study, undamaged liposomes fuse with the cell membrane only 1.5-2 hours after binding to the cell surface, and then, the components of liposomal bilayer enter the cell separately. The study on the time course of plasma concentration in mice showed that the area under the curve of MTX generated upon intravenous injection of MTX-DG liposomes exceeded that of intact MTX 2.5-fold. These data suggested the advantage of using liposomal formulation to treat systemic manifestation of hematological malignancies. Indeed, the administration of MTX-DG liposomes to recipient mice bearing T-cell leukemic lymphoma using a dose-sparing regimen resulted in lower toxicity and retarded lymphoma growth rate as compared with MTX.

    ID:1796
  2. Алексеева А.С., Третьякова Д.С., Мельникова Д.Н., Молотковский Юл.Г., Болдырев И.А. (2016). Новый флуоресцентный мембранный зонд (2,3;5,6 бисциклогексил)bodipy меченный фосфатидилхолн. Биоорг. хим. 42 (3), 339–344 [+]

    Новый мембранный зонд бисциклогексил BODIPY (BCHB) меченный фосфатидилхолин структурно очень близок в 1,3,5,7 тетраметил BODIPY (TMB) меченному фосфатидилхолину и синтезируется по аналогичной схеме. Системы сопряженных связей BCHB и TMB формально идентичны, однако спектральные характеристики BCHB заметно отличаются, что делают BCHB хорошим акцептором фёрстеровского резонансного переноса (FRET) для TMB. Показано, что FRET пара фосфатидилхолинов на основе BCHB и TMB является перспективным инструментом для исследования мембранных систем, например, межмембранного липидного переноса.
     

    ID:1498
  3. Malinina L., Simanshu D.K., Zhai X., Samygina V.R., Kamlekar R., Kenoth R., OchoaLizarralde B., Malakhova M.L., Molotkovsky J.G., Patel D.J., Brown R.E. (2015). Sphingolipid transfer proteins defined by the GLTP-fold. Q. Rev. Biophys. 48 (3), 281–322 [+]

    Glycolipid transfer proteins (GLTPs) originally were identified as small (~24 kDa), soluble, amphitropic proteins that specifically accelerate the intermembrane transfer of glycolipids. GLTPs and related homologs now are known to adopt a unique, helically dominated, two-layer 'sandwich' architecture defined as the GLTP-fold that provides the structural underpinning for the eukaryotic GLTP superfamily. Recent advances now provide exquisite insights into structural features responsible for lipid headgroup selectivity as well as the adaptability of the hydrophobic compartment for accommodating hydrocarbon chains of differing length and unsaturation. A new understanding of the structural versatility and evolutionary premium placed on the GLTP motif has emerged. Human GLTP-motifs have evolved to function not only as glucosylceramide binding/transferring domains for phosphoinositol 4-phosphate adaptor protein-2 during glycosphingolipid biosynthesis but also as selective binding/transfer proteins for ceramide-1-phosphate. The latter, known as ceramide-1-phosphate transfer protein, recently has been shown to form GLTP-fold while critically regulating Group-IV cytoplasmic phospholipase A2 activity and pro-inflammatory eicosanoid production.

    ID:1480
  4. Trusova V.M., Molotkovsky J.G., Kinnunen P.K.J., Gorbenko G.P. (2014). Structural aspects of cytochrome c – cardiolipin interactions: Förster resonance energy transfer study. , 173–223 [+]

    Cytochrome c (cyt c) is a mitochondrial membrane hemoprotein of high physiological importance. Fisrt, cyt c is one of the key elements of respiration chain transferring electrons from cyt c reductase (bc1 complex) to cyt c oxidase. Second, release of cyt c from the intermembrane space of mitochondria into the cytosol triggers the apoptotic pathway. The idea that specific interactions between cyt c and cardiolipin (CL), the main lipid component of mitochondrial membrane, are crucial to the protein biological activities, constantly receives further corroboration from both theoretical and experimental studies. Despite considerable progress achieved in the field of cyt c – CL biophysics, the detailed structural description of protein-lipid complexation is still lacking. In the present study we applied Förster resonance energy transfer (RET) technique to give comprehensive characterization of cyt c binding to the model lipid membranes composed of the mixtures of zwitterionic lipid phosphatidylcholine (PC) with anionic lipids phosphatidylglycerol (PG), phosphatidylserine (PS) or cardiolipin (CL) in different molar ratios. The donor-acceptor pairs were represented by either anthrylvinyl-labeled PC (AV-PC) or anthrylvinyl-labeled CL (AV-CL) incorporated in trace amounts in lipid vesicles, and heme moiety of cyt c. Association of the protein with the lipid bilayers led to the decrease in donor fluorescence reflecting energy transfer from AV fluorophore to heme. The most effective RET was found for CL-containing membranes. This observation has been interpreted in terms of higher affinity of cyt c to CL as compared to other anionic lipids. In order to get understanding of protein specificity to CL, RET was measured as a function of CL content and ionic strength. Monte Carlo analysis of multiple datasets revealed a complex interplay between several processes, namely i) lipid demixing; ii) CL transition into extended conformation; iii) formation of hexagonal phase. The switch between these states was found to be controlled by CL content and salt concentration. These characteristics of cyt c – CL interaction are of great interest not only in the context of regulating cyt c electron transfer and apoptotic propensities, but also from the viewpoint of the protein biogenesis.

    ID:1149
  5. Zhytniakivska O., Trusova V., Gorbenko G., Kirilova E., Kalnina I., Kirilov G., Molotkovsky J., Tulkki J., Kinnunen P. (2014). Location of novel benzanthrone dyes in model membranes as revealed by resonance energy transfer. J Fluoresc 24 (3), 899–907 [+]

    Förster resonance energy transfer (FRET) between anthrylvinyl-labeled phosphatidylcholine (AV-PC) as a donor and newly synthesized benzanthrones (referred to here as A8, A6, AM12, AM15 and AM18) as acceptors has been examined to gain insight into molecular level details of the interactions between benzanthrone dyes and model lipid membranes composed of zwitterionic lipid phosphatidylcholine and its mixtures with anionic lipids cardiolipin (CL) and phosphatidylglycerol (PG). FRET data were quantitatively analyzed in terms of the model of energy transfer in two-dimensional systems taking into account the distance dependence of orientation factor. Evidence for A8 location in phospholipid headgroup region has been obtained. Inclusion of CL and PG into PC bilayer has been found to induce substantial relocation of A6, AM12, AM15 and AM18 from hydrophobic membrane core to lipid-water interface.

    ID:1148
  6. Simanshu D.K., Zhai X., Munch D., Hofius D., Markham J.E., Bielawski J., Bielawska A., Malinina L., Molotkovsky J.G., Mundy J.W., Patel D.J., Brown R.E. (2014). Arabidopsis accelerated cell death 11, ACD11, is a ceramide-1-phosphate transfer protein and intermediary regulator of phytoceramide levels. Cell Rep 6 (2), 388–99 [+]

    The accelerated cell death 11 (acd11) mutant of Arabidopsis provides a genetic model for studying immune response activation and localized cellular suicide that halt pathogen spread during infection in plants. Here, we elucidate ACD11 structure and function and show that acd11 disruption dramatically alters the in vivo balance of sphingolipid mediators that regulate eukaryotic-programmed cell death. In acd11 mutants, normally low ceramide-1-phosphate (C1P) levels become elevated, but the relatively abundant cell death inducer phytoceramide rises acutely. ACD11 exhibits selective intermembrane transfer of C1P and phyto-C1P. Crystal structures establish C1P binding via a surface-localized, phosphate headgroup recognition center connected to an interior hydrophobic pocket that adaptively ensheaths lipid chains via a cleft-like gating mechanism. Point mutation mapping confirms functional involvement of binding site residues. A π helix (π bulge) near the lipid binding cleft distinguishes apo-ACD11 from other GLTP folds. The global two-layer, α-helically dominated, "sandwich" topology displaying C1P-selective binding identifies ACD11 as the plant prototype of a GLTP fold subfamily.

    ID:1147
  7. Simanshu D.K., Kamlekar R.K., Wijesinghe D.S., Zou X., Zhai X., Mishra S.K., Molotkovsky J.G., Malinina L., Hinchcliffe E.H., Chalfant C.E., Brown R.E., Patel D.J. (2013). Non-vesicular trafficking by a ceramide-1-phosphate transfer protein regulates eicosanoids. Nature 500 (7463), 463–7 [+]

    Phosphorylated sphingolipids ceramide-1-phosphate (C1P) and sphingosine-1-phosphate (S1P) have emerged as key regulators of cell growth, survival, migration and inflammation. C1P produced by ceramide kinase is an activator of group IVA cytosolic phospholipase A2α (cPLA2α), the rate-limiting releaser of arachidonic acid used for pro-inflammatory eicosanoid production, which contributes to disease pathogenesis in asthma or airway hyper-responsiveness, cancer, atherosclerosis and thrombosis. To modulate eicosanoid action and avoid the damaging effects of chronic inflammation, cells require efficient targeting, trafficking and presentation of C1P to specific cellular sites. Vesicular trafficking is likely but non-vesicular mechanisms for C1P sensing, transfer and presentation remain unexplored. Moreover, the molecular basis for selective recognition and binding among signalling lipids with phosphate headgroups, namely C1P, phosphatidic acid or their lyso-derivatives, remains unclear. Here, a ubiquitously expressed lipid transfer protein, human GLTPD1, named here CPTP, is shown to specifically transfer C1P between membranes. Crystal structures establish C1P binding through a novel surface-localized, phosphate headgroup recognition centre connected to an interior hydrophobic pocket that adaptively expands to ensheath differing-length lipid chains using a cleft-like gating mechanism. The two-layer, α-helically-dominated 'sandwich' topology identifies CPTP as the prototype for a new glycolipid transfer protein fold subfamily. CPTP resides in the cell cytosol but associates with the trans-Golgi network, nucleus and plasma membrane. RNA interference-induced CPTP depletion elevates C1P steady-state levels and alters Golgi cisternae stack morphology. The resulting C1P decrease in plasma membranes and increase in the Golgi complex stimulates cPLA2α release of arachidonic acid, triggering pro-inflammatory eicosanoid generation.

    ID:893
  8. Kuznetsova N.R., Svirshchevskaya E.V., Skripnik I.V., Zarudnaya E.N., Benke A.N., Gaenko G.P., Molotkovskiĭ Yu.G., Vodovozova E.L. (2013). Interaction of liposomes bearing a lipophilic doxorubicin prodrug with tumor cells. Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology 7 (1), 12–20 [+]

    When used as nanosized carriers, liposomes enable targeted delivery and decrease systemic toxicity of antitumor agents significantly. However, slow unloading of liposomes inside cells diminishes the treatment efficiency. The problem could be overcome by the adoption of lipophilic prodrugs tailored for incorporation into lipid bilayer of liposomes. We prepared liposomes of egg yolk phosphatidylcholine and yeast phosphatidylinositol bearing a diglyceride conjugate of an antitumor antibiotic doxorubicin (a lipophilic prodrug, DOX-DG) in the membrane to study how these formulations interact with tumor cells. We also prepared liposomes of rigid bilayer-forming lipids, such as a mixture of dipalmitoylphosphatidylcholine and cholesterol, bearing DOX in the inner water volume, both pegylated (with polyethylene glycol (PEG) chains exposed to water phase) and non-pegylated. Efficiency of binding of free and liposomal doxorubicin with tumor cells was evaluated in vitro using spectrofluorimetry of cell extracts and flow cytometry. Intracellular traffic of the formulations was investigated by confocal microscopy; co-localization of DOX fluorescence with organelle trackers was estimated. All liposomal formulations of DOX were shown to distribute to organelles retarding its transport to nucleus. Intracellular distribution of liposomal DOX depended on liposome structure and pegylation. We conclude that the most probable mechanism of the lipophilic prodrug penetration into a cell is liposome-mediated endosomal pathway.

    ID:996
  9. Kuznetsova N., Kandyba A., Vostrov I., Kadykov V., Gaenko G., Molotkovsky J., Vodovozova E. (2009). Liposomes loaded with lipophilic prodrugs of methotrexate and melphalan as convenient drug delivery vehicles. J. Drug. Deliv. Sci. Techn. 19, 51–59 [+]

    Liposomal formulations prepared by extrusion from natural phospholipids and 1,2-dioleoylglycerol conjugates of methotrexate and melphalan (egg phosphatidylcholine–phosphatidylinositol–prodrug, 8:1:1, by mol.) were characterized by size, composition and stability. Both prodrugs were shown to incorporate completely into unilamellar liposomes with the mean size below 100 nm and form stable dispersions containing the drug concentrations relevant for systemic injections in animals. For long-term storage, the dispersions can be  subjected to deep freezing (- 196°C) and stored at - 70°C; before usage, they should be defrosted and treated shortly in an ultrasonic bath. According to the example of methotrexate conjugate, stability of prodrug ester bond in liposomal formulation towards hydrolysis by human plasma esterases during 24-h incubation were established. Also, liposomes bearing methotrexate conjugate were shown to overcome resistance of human leukemia cells related to impaired transport of initial drug across the membrane.

    ID:106
  10. Boldyrev I.A., Gaenko G.P., Moiseeva E.V., Deligeorgiev T., Kaloianova S., Lesev N., Vasilev A., Molotkovskiĭ Iu.G. (2009). [1,10-phenantroline europium complexes: their inclusion in liposomes and cytotoxicity]. Bioorg. Khim. 37 (3), 408–13 [+]

    For a series of 1,10-phenantroline tris-beta-diketonate europium complexes (EuC), cytotoxic activity on the HBL-100 human breast carcinoma cells was determined. Liposomal preparation of the most active EuC, V12, was also tested for cytotoxicity. Testing of this preparation in vivo on starting lethal murine model of T cell leukemic lymphoma ASF-LL showed that the inclusion of V12 in liposomes did not increase its antitumour activity in a local mode of administration.

    ID:639
  11. Vodovozova E.L., Pazynina G.V., Tuzikov A.B., Grechishnikova I.V., Molotkovsky J.G. (2009). Synthesis of photoreactive inorganic probes--instruments for studying membrane lectins. Bioorg. Khim. 30 (2), 174–81 [+]

    A method for the synthesis of photoaffinity neoglycolipid probes with a highly efficient carbene-generating diazocyclopentadien-2-ylcarbonyl (Dcp) label, which can be radioiodinated under standard oxidation conditions, was developed. The probes are intended for incorporation into the lipid bilayer. They are lipophilic glycoconjugates on the basis of an amphiphilic aglycone built up from a diacylglycerol and a polyethylene glycol spacer (with a polymerization degree of 9-16) bearing the Dcp label at the terminal unit. The location of the label in the aglycone provides the possibility of one-step preparation of a wide range of probes using various carbohydrate synthons. We have synthesized photoaffinity neoglycoconjugates containing the oligosaccharides: sialyl LewisX tetrasaccharide and A trisaccharide, which is specific to some tumor cells. A probe containing an inactive pentaol (aminodeoxyglucitol) was also synthesized to detect nonspecific binding. The Dcp label is bound to the probe molecule by ester bond; its lability under alkaline conditions facilitates the analysis of cross-linked products after photoaffinity labeling. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 2; see also http://www.maik.ru.

    ID:242
  12. 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.

    ID:214
  13. Vodovozova E.L., Tsibizova E.V., Molotkovsky J.G. (2001). One-step iodination of the diazocyclopentadien-2-ylcarbonyl group—a new and convenient preparation of effective radiolabelled photoaffinity probes. J. Chem. Soc., Perkin Trans. 1  (200), 2221–2228 [+]

    A detailed study devoted to direct iodination of the photoactivatable diazocyclopentadien-2-ylcarbonyl (Dcp) group is presented. The iodination does not influence the high carbene reactivity of the Dcp-generated carbene. It was shown that the Dcp substituent forms 4-mono-, 5-mono- and 4,5-diiododerivatives upon iodination under oxidative conditions (76, 20 and 4%, respectively, when DcpOMe 2 is iodinated). Photolysis of the individual products of iodination in cyclohexane resulted in rather high insertion into non-activated CH bonds, without noticeable loss of iodine. Syntheses of new phospholipid and ganglioside membrane probes are also described which incorporate the Dcp function via a labile ester bond. A [125I]-Dcp-phosphatidylcholine probe exhibiting high specific radioactivity (∼500 Ci mmol1) was easily prepared at yields of 90% (on the starting Na125I), by using peracetic acid as an oxidant.
    Furthermore, it was successfully used for photolabelling of the integral protein hemagglutinin in a well-characterised influenza virus model. In summary, the Dcp group is efficient for labelling a wide variety of molecules, and as such, it provides a new tool for exploring a diverse range of biological systems.

    ID:182
  14. Vodovozova E.L., Moiseeva E.V., Grechko G.K., Gayenko G.P., Nifant'ev N.E., Bovin N.V., Molotkovsky J.G. (2000). Antitumour activity of cytotoxic liposomes equipped with selectin ligand SiaLe(X), in a mouse mammary adenocarcinoma model. Eur. J. Cancer 36 (7), 942–9 [+]

    The overexpression of lectins by malignant cells compared with normal ones can be used for the targeting of drug-loaded liposomes to tumours with the help of specific carbohydrate ligands (vectors). Recently we have shown that liposomes bearing specific lipid-anchored glycoconjugates on a polymeric matrix bind in vitro to human malignant cells more effectively and, being loaded with a lipophilic prodrug of merphalan, reveal higher cytotoxic activity compared with unvectored liposomes. In this study, carbohydrate-equipped cytotoxic liposomes were tested in vivo in a mouse breast cancer model, BLRB-Rb (8.17)1Iem strain with a high incidence of spontaneous mammary adenocarcinoma (SMA). Firstly, a cell line of the SMA was established which was then used to determine the specificity of the tumour cell lectins. After screening of the lectin specificity of a number of fluorescent carbohydrate probes, SiaLe(X) was shown to be the ligand with the most affinity, and a lipophilic vector bearing this saccharide was synthesised. Then different liposomal formulations of the synthetic merphalan lipid derivative and SiaLe(X) vector were prepared and applied in the treatment of mice with grafted adenocarcinomas. The results of the tumorigenesis data show that the therapeutic efficacy of merphalan increases sharply after its insertion as a lipophilic prodrug into the membrane of SiaLe(X)-vectored liposomes.

    ID:109
  15. Vodovozova E.L., Gayenko G.P., Razinkov V.I., Korchagina E.Y., Bovin N.V., Molotkovsky J.G. (1998). Saccharide-assisted delivery of cytotoxic liposomes to human malignant cells. Biochem. Mol. Biol. Int. 44 (3), 543–53 [+]

    The overexpression of lectins by malignant cells was applied for in vitro targeting of liposomes equipped with a saccharide vector and loaded in the lipid phase with a lipid derivative of anticancer agent sarcolysine. The lectin specificity of human leukemia HL-60 and human lung adenocarcinoma ACL cells was revealed by tests with fluorescein-labeled sugar probes. With the help of fluorescent lipid dye it was shown that active saccharide ligands increased the level of the vectored liposome binding to malignant cells by 50-80% as compared to liposomes without vector or with inactive one. The degree of liposome/cell membrane fusion was monitored fluorometrically and was shown to be complete and independent of the vectors. The targeted drug-loaded liposomes had the cytotoxic activity 2-4 times higher as compared to the vector-free ones.

    ID:110
  16. Bergelson L.D., Molotkovsky J.G., Manevich Y.M. (1985). Lipid-specific fluorescent probes in studies of biological membranes. Chem. Phys. Lipids 37 (2), 165–95 [+]

    Lipid-specific fluorescent probes are natural lipids carrying an apolar fluorophore in one of the hydrocarbon chains. Since such probes retain the head groups and resemble the molecular shape of native membrane lipids, they largely mimic the behaviour of their natural prototypes in biological membranes. Information provided by the lipid-specific probes is more differentiated and easier to interpret than that obtained from non-lipid probes. The principles of design of lipid-specific probes are formulated and the relative advantages and disadvantages of various fluorophores are discussed. In order to reduce ambiguities caused by perturbation of the probe environment, it is proposed to use, in a comparative manner, two or more lipid-specific probes resembling each other in all aspects except the polar head groups (the 'two probes' concept). Two types of fluorophores, the anthrylvinyl group and the perylenoyl group, were found to be well suited for the synthesis of lipid-specific probes. Use of both types of probes 'in tandem' opens new possibilities for studying lipid-protein and lipid-lipid interactions in biological membranes. The anthrylvinyl- and perylenoyl-labeled lipids were applied in studies of serum lipoproteins and erythrocyte membranes. A new highly sensitive ligand-receptor binding assay and a new approach to biological signal amplifying based on the use of lipid-specific probes are described.

    ID:221
  17. Molotkovsky J.G., Manevich Y.M., Babak V.I., Bergelson L.D. (1984). Perylenoyl- and anthrylvinyl-labeled lipids as membrane probes.  (778), 281–288 ID:215
  18. Molotkovsky J.G., Bergelson L.D. (1973). Synthesis of unsaturated mixed acid phosphatidylinositol of natural configuration. A new procedure for resolving racemic alcohols.  (11), 135–147 ID:216