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1.
Gracheva I. A. Tretiakova D. S. Zamyshlyaeva O. G. Kudriashova E. S. Vodovozova E. L. Fedorov A. Y. Boldyrev I. A. 《Russian Journal of Bioorganic Chemistry》2021,47(5):1114-1117
Russian Journal of Bioorganic Chemistry - Fluorescent lipid probes are widely used as tools for studying the properties of biological membranes and for studies of such biological functions of... 相似文献
2.
N. R. Kuznetsova E. V. Svirshchevskaya N. S. Sitnikov L. Abodo H. Sutorius J. Zapke J. Velder P. Thomopoulou H. Oschkinat A. Prokop H. -G. Schmalz A. Yu. Fedorov E. L. Vodovozova 《Russian Journal of Bioorganic Chemistry》2013,39(5):543-552
Colchicine site binders—blockers of tubulin polymerization—are potential antimitotic agents for anticancer therapy. To reduce their systemic toxicity and improve biodistribution, encapsulation in nanosized liposomes may be employed. Liposomes present a convenient means for preparation of injectable for-mulations of hydrophobic compounds, however colchicine as such is known to leak through the lipid bilayer. In this study, newly synthesized triazole-containing analogues of colchicine and allocolchicine, and their palmitic and oleic esters (lipophilic prodrugs) were tested for anti-proliferative activity and apoptosis-inducing potential. In contrast to colchicine conjugates, whose activities ranged with those of colchicine, allocolchicine derivatives exhibited drastically lower effects and were discarded. Liposomes of about 100 nm in diameter composed of egg phosphatidylcholine-yeast phosphatidylinositol-palmitic or oleic prodrug, 8: 1: 1, by mol, were prepared by standard extrusion technique and tested in a panel of four human tumor cell lines. Liposome formulations preserved the biological activities of the parent colchicinoid the most towards human epithelial tumor cells. Moreover, liposomal form of the oleoyl bearing colchicinoid inhibited cell proliferation more efficiently than free lipophilic prodrug. Due to substantial loading capacity of the liposomes, the dispersions contain sufficient concentration of the active agent to test wide dose range in experiments on systemic administration to animals. 相似文献
3.
N. R. Kuznetsova E. V. Svirshchevskaya I. V. Skripnik E. N. Zarudnaya A. N. Benke G. P. Gaenko Yu. G. Molotkovskii E. L. Vodovozova 《Biochemistry (Moscow) Supplemental Series A: Membrane and Cell Biology》2013,7(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. 相似文献
4.
Zaitseva L. G. Ovchinnikova T. V. Vodovozova E. L. Molotkovsky Yul. G. Polyakov N. B. Titov M. I. Esipov S. E. Grinkevich V. A. 《Russian Journal of Bioorganic Chemistry》2002,28(5):371-384
The subunits of the F0 membrane sector of bovine heart mitochondrial H+-ATPase that contact the lipids of the mitochondrial inner membrane were identified with the use of specially synthesized proteoliposomes that contained active mitochondrial H+-ATPase and a photoreactive lipid, which was 1-acyl-2-[12-[di-azocyclopentadiene-2-carbonylamino)-[12-14C]dodecanoyl]-sn-glycero-3-phosphocholine, 1-acyl-2-[11-([125I]diazoiodocyclopentadiene-2-carbonyloxy)undecanoyl]-sn-glycero-3-phosphocholine, or 1-acyl-2-[12-(diazocyclopentadiene-2-carbonylamino)dodecanoyl]-sn-glycero-3-phosphocholine, where acyl is a mixture of the residues of palmitic (70%) and stearic (30%) acids. An analysis of the cross-linked products obtained upon the UV-irradiation of these proteoliposomes indicated that subunits c and a of the F0 membrane sector contact the lipids. The crosslinked products were identified by SDS-PAGE and MALDI mass spectrometry. 相似文献
5.
E. V. Moiseeva N. R. Kuznetsova E. V. Svirshchevskaya N. V. Bovin N. S. Sitnikov A. S. Shavyrin I. P. Beletskaya S. Combes A. Yu. Fedorov E. L. Vodovozova 《Biochemistry (Moscow) Supplemental Series B: Biomedical Chemistry》2011,5(3):276-283
The antimitotic agent combretastatin A-4 (CA-4) has been recently proposed as an antivascular agent for anticancer therapy.
In order to reduce systemic toxicity by means of administration in liposome formulations, new lipophilic prodrugs, oleic derivatives
of CA-4 and its 4-arylcoumarin analogue (CA4-Ole and ArC-Ole, respectively), have been synthesized in this study. Liposomes
with mean diameter of 100 nm prepared on the basis of egg phosphatidylcholine and baker’s yeast phosphatidylinositol quantitatively
included up to 15 mol% of CA4-Ole, or 7 mol% of ArC-Ole. To achieve targeting to neovascular endothelium prodrug bearing liposomes
decorated with the tetrasaccharide selectin ligand Sialyl Lewis X (SiaLeX) have been also prepared. The antitumor activity
was studied in vivo using the model of slow-growing mouse breast cancer. Under the dose used (22 mg/kg) and the administration
protocol (four injections, one per a week, starting from the appearance of palpable tumors) cytostatic CA-4 did not reveal
any anticancer effect; moreover, it even stimulated tumor growth. The liposome formulations of CA4-Ole did not demonstrate
such stimulation. However, to achieve a pronounced antitumor effect, the number of injections of liposomes should be apparently
increased. The cytotoxic activity of a novel antimitotic agent ArC was one order of magnitude lower in the human breast carcinoma
cell culture in vitro. Nevertheless, in vivo in the mouse model of breast cancer the antitumor effect of this compound corresponded
to the double equivalent dose of CA-4. The results demonstrate perspectives of SiaLeX-liposomes loaded with ArC-Ole: the preparation partially inhibited tumor growth already after the second injection. Thus,
subsequent optimization of doses and regimens of administration both for ArC and liposomal ArC-Ole formulations are needed. 相似文献
6.
7.
E M Manevich M A Martynova G I Muzya E L Vodovozova J G Molotkovsky L D Bergelson 《Biochimica et biophysica acta》1988,963(2):302-310
The interaction of human serum low-density lipoproteins (LDL) with various types of prostaglandins (PG) was studied using equilibrium dialysis, steady-state fluorescence polarization spectroscopy and photolabeling methods. Low concentrations (10(-13)-10(-9) M) of PGE1 and PGF2 alpha were shown to induce specific rearrangements of the lipids on the LDL surface, whereas the closely related PGE2 and PGF1 alpha had no effect. With fluorescent labeled LDL, the PGE1-induced changes of the steady-state fluorescence polarization (P) were shown to be time- and concentration-dependent, saturable and reversible. However, equilibrium dialysis revealed a very low binding capacity of LDL for PGE1 (approx. 1 prostaglandin molecule per 600 LDL particles). Approximately the same PGE1 concentration was sufficient to cause maximal changes of P, to enhance the binding to apolipoprotein B of a photoreactive sphingomyelin analogue inserted into the LDL surface and to alter the thermal phase behavior of the LDL surface lipids. It is proposed that the LDL surface rearrangement caused by prostaglandins is due to the interaction of prostaglandins with apolipoprotein B, resulting in formation of short-lived complexes. The mechanism of this interaction is discussed in terms of the non-equilibrium ligand-receptor interaction model proposed earlier to explain the interaction of prostaglandins with high-density lipoproteins (Bergelson, L.D. et al. (1987) Biochim. Biophys. Acta 921, 182-190). It is suggested that direct prostaglandin-lipoprotein interactions may play a role in the homeostasis of cholesterol. 相似文献
8.
A G Bukrinskaya J G Molotkovsky E L Vodovozova Y M Manevich L D Bergelson 《Biochimica et biophysica acta》1987,897(2):285-292
The membrane structures of remantadin-sensitive and remantadin-resistant influenza virus strains were studied using a photoreactive fatty acid as well as analogues of phosphatidylcholine, phosphatidylethanolamine and sphingomyelin, carrying a fluorescent or photoreactive reporter group at the end of one of the aliphatic chains. The results obtained demonstrated for the first time that the phospholipids of the viral membrane form lateral domains differing by the fluidity of their hydrocarbon chains and, probably, by the head-group composition of the lipids. The hemagglutinin small subunit (HA2) was shown to protrude into the apolar region of the phospholipid bilayer, whereas the M1 protein makes contact only with the inner surface. In the remantadin-sensitive virions the heavy hemagglutinin chain (HA1) appears not to be in contact with the lipid bilayer, whereas in the remantadin-resistant strain HA1 has a hydrophobic segment that proved to be inserted into the bilayer. 相似文献
9.
Zaĭtseva LG Ovchinnikova TV Vodovozova EL Molotkovskĭ IuG Poliakov NB Titov MI Esipov SE Grinkevich VA 《Bioorganicheskaia khimiia》2002,28(5):411-425
The subunits of the F0 membrane sector of bovine heart mitochondrial H(+)-ATPase that contact the lipids of the mitochondrial inner membrane were identified with the use of specially synthesized proteoliposomes that contained active mitochondrial H(+)-ATPase and a photoreactive lipid, which was 1-acyl-2-[12-(diazocyclopentadiene-2-carbonylamino)-[12-14C]dodecanoyl]-sn- glycero-3-phosphocholine, 1-acyl-2-[11-([125I]diazoiodocyclopentadiene-2-carbonyloxy)undecanoyl]-sn- glycero-3-phosphocholine, or 1-acyl-2-[12-(diazocyclopentadiene-2-carbonylamino)dodecanoyl]-sn-glycero- 3-phosphocholine, where acyl is a mixture of the residues of palmitic (70%) and stearic (30%) acids. An analysis of the cross-linked products obtained upon the UV-irradiation of these proteoliposomes indicated that subunits c and a of the F0 membrane sector contact the lipids. The cross-linked products were identified by SDS-PAGE and MALDI mass spectrometry. 相似文献
10.
Vodovozova EL Kuznetsova NR Gaenko GP Molotkovskiĭ IuG 《Bioorganicheskaia khimiia》2007,33(4):470-473
We have recently synthesized a lipid conjugate of the anticancer agent methotrexate (MTX-DG) and showed that the conjugate is quantitatively included in the lipid bilayer of liposomes prepared by a standard extrusion technique from an 8 : 1 : 1 (mol) egg phosphatidylcholine-yeast phosphatidylinositol-MTX-DG mixture. Both the size of liposomes (126 +/- 30 nm) and the MTX-DG concentration (4.4 mM) are relevant for systemic injections in mammals. The liposomal formulation of MTX-DG was shown to overcome the resistance of tumor cells in vitro to methotrexate: the cytotoxic activities (IC50) of MTX in cultures of the human T-lymphoblastic leukemia cell line CEM-CCRF and the MTX-resistant subline CEM/MTX were 0.075 +/- 0.005 and 16.4 +/- 4.9 microM, respectively, while, in the case of liposomes loaded with MTX-DG, the IC50 values were much closer: 0.77 +/- 0.06 and 3.8 +/- 1.9 microM. 相似文献