[Some regularities of dimer II formation in BODIPY-FL-labeled lipids].

Some regularities of dimer II formation from BODIPY-FL-labeled lipid probes using mono-, bis-, and tris-BODIPY-FL derivatives of gangliosides G(M1) and G(D1a) and mono- and bis-BODIPY-FL derivatives of triglycerides have been defined. BODIPY-FL-labeled glycolipids were shown in phospholipid layers to reveal a greater disposition towards dimer II formation than BODIPY-FL-labeled glycerides. The formation of dimer 11 was also shown to depend on the label position in the probe molecule. Probes bearing a label in the polar head area are more prone to dimer II formation than probes labeled in the apolar part of the molecule.

Conjugates of oligonucleotides with polyaromatic fluorophores as promising DNA probes.

Conjugates of pyrene and perylene with oligodeoxynucleotides were synthesized and tested as hybridisation probes. A 13-mer containing a 3-peryleneacetic acid residue attached to the 5' end through a hexamethylenediamine linker showed no response in the fluorescent spectrum upon hybridisation to the complementary sequence. At the same time, pyrene-labelled probes are sensitive to duplex formation. A pyrene pseudonucleotide unit based on 4-(1-pyrenyl)-1,3-butanediol can be introduced into any predetermined position(s) of the oligonucleotide chain. The probes polylabelled in this fashion displayed considerable changes in the excimer-to-monomer fluorescence intensity ratio after duplex formation. The internal location of two pyrene residues in the probe provides a drastic enhancement of excimer fluorescence (approximately 470 nm) upon hybridisation. When two pyrene units were brought into close proximity to two pyrenes in the complementary strand upon duplex formation, strong excimer emission at approximately 450 nm was detected. This effect provides a basis for a sensor construction designed to detect nucleic acid hybridisation.

[Synthesis and characteristics of fluorescent BODIPY-labeled gangliosides]. / Sintez i svoistva fluorestsentnykh BODIPY-mechenykh gangliozidov.

A series of new fluorescent-labeled gangliosides bearing the residues of acids labeled by 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) in the polar or/and apolar moiety were synthesized. These are ganglioside GM1 labeled with the residue of 4,4-difluoro-4-bora-3a,4a-diaza-5,7-dimethyl-s-indacenyl-3-propanoic BODIPY-FL-propanoic) and -indacenyl-5-pentanoic (BODIPY-FL-pentanoic) acid in the oligosaccharide moiety of the molecule, and ganglioside GD1a labeled with two residues of BODIPY-FL-pentanoic acid in the oligosaccharide moiety and also with the residue of BODIPY-FL-pentanoic acid and the residue of 4,4-difluoro-4-bora-3a,4a-diaza-5-octyl-s-indacenyl-5-pentanoic acid in the ceramide part of the molecule. Some spectral characteristics and the behavior in the model membrane systems of the synthesized probes were studied. In their emission spectra, the BODIPY-labeled gangliosides included into phosphatidylcholine liposomes at high concentrations (> 1 mol %) exhibit a long-wavelength maximum (at approximately 630 nm) in addition to the usual maximum (at 510-515 nm).

[The synthesis of new photoaffinity probes on the basis of ganglioside GM1]. / Sintez novykh fotoreaktivnykh zondov na osnove gangliozida GM1.

New photoaffine probes, photoreactive derivatives of ganglioside GM1 bearing a carbene-generating diazocyclopentadien-2-ylcarbonyl group at various distances from the carbohydrate moiety in their molecules, were synthesized.

[A new oxa-analog of myristic acid, suppressing replication of the human immunodeficiency virus]. / Novyi oksaanalog miristinovoi kisloty, podavliaiushchii replikatsiiu virusa immunodefitsita cheloveka.

A series of oxaanalogs of myristic acid were synthesized and tested for antiviral activity in MT4 cells infected with human immunodeficiency virus 1 (HIV-1). The synthesized acids have no toxic effect on uninfected MT4 cells at a concentration of 100 microM. 14,14,14-Trifluoro-12-oxatetradecanoic acid substantially (by 75%) inhibits the reproduction of HIV-1. Other compounds synthesized, (7Z)-13-, (9Z)-13-, and (7Z)-11-oxatetradecenoic acids, exhibit no antiviral effect.

[Lipid derivatives of sarcolysin, methotrexate and rubomycin]. / Lipidnye proizvodnye sarkolizina, metotreksata i rubomitsina]

To change the pharmacokinetic properties of the known antitumor agents sarcolysine, rubomycin, and methotrexate, their lipid derivatives were synthesized with the residues of rac-1,2-dioleoylglycerol and heptadecyl alcohol. An ether lipid analog, 3-sarcolysyl 2-methyl-1-octadecyl-sn-glycerol, with the lipid moiety being itself an antineoplastic agent was also obtained.

[Transportation of cytotoxic liposomes to malignant cells using a carbohydrate determinant]. / Transportirovka tsitotoksicheskikh liposom k zlokachestvennym kletkam s pomoshch'iu uglevodnykh determinant.

A method of the synthesis of lipophilic glycoconjugates (vectors) on the basis of polyethyleneglycol-containing detergent was proposed. It has been shown by flow cytofluorometry that fluorescent labeled liposomes equipped with beta-galactosyl conjugate are bound human leukosis HL-60 cells more effectively than liposomes embedded with the beta-glucosyl conjugate or vector-free liposomes. A new lipid derivative of antitumor drug rubomycin (daunorubicin), N-(rac-1,2-dioleoylglycero-3-oxalyl)rubomycin (RubDG) has been synthesized. Liposomes loaded with RubDG and equipped with galactosyl vector showed higher cytotoxic activity in vitro against HL-60 cells than analogous unvectored liposomes or liposomes bearing glucosyl conjugate.

[Gangliosides from human placenta]. / Gangliozidy platsenty cheloveka.

Gangliosides of human placenta were studied, using biochemical methods and specific antibodies. The placenta was found to contain three types of gangliosides with oligosaccharide chains Lac, GgOse4 and nLcOse4.

Gangliosides induce cell apoptosis in the cytotoxic line CTLL-2, but not in the promyelocyte leukemia cell line HL-60.

Gangliosides induce apoptosis in the cells of the IL-2-dependent cytotoxic mouse line CTLL-2. Upon incubation with gangliosides for 24 h, their effect resulting in appearance of apoptotic cells, falls in a series GM2 > GM3 > GM1 > GD1a > GD1b > GT1b. In the presence of rIL-2, apoptosis induced by GM1 is suppressed, whereas that induced by GM2 is enhanced (the effect of intracellular agent C2-Cer is independent of this cytokine). The GM1-induced apoptosis is cancelled by the caspase I inhibitor. The gangliosides under study are not able to induce apoptosis in the promyelocyte leukemia cell line HL-60. Physiological aspects of the phenomenon found are discussed.