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Rostislav A. Petrov Svetlana Yu. Maklakova Yan A. Ivanenkov Stanislav A. Petrov Olga V. Sergeeva Emil Yu. Yamansarov Irina V. Saltykova Igor I. Kireev Irina B. Alieva Ekaterina V. Deyneka Alina A. Sofronova Anastasiia V. Aladinskaia Alexandre V. Trofimenko Renat S. Yamidanov Sergey V. Kovalev Victor E. Kotelianski Timofey S. Zatsepin Elena K. Beloglazkina Alexander G. Majouga 《Bioorganic & medicinal chemistry letters》2018,28(3):382-387
Asialoglycoprotein receptor (ASGP-R) is a promising biological target for drug delivery into hepatoma cells. Nevertheless, there are only few examples of small-molecule conjugates of ASGP-R selective ligand equipped by a therapeutic agent for the treatment of hepatocellular carcinoma (HCC). In the present work, we describe a convenient and versatile synthetic approach to novel mono- and multivalent drug-conjugates containing N-acetyl-2-deoxy-2-aminogalactopyranose and anticancer drug – paclitaxel (PTX). Several molecules have demonstrated high affinity towards ASGP-R and good stability under physiological conditions, significant in vitro anticancer activity comparable to PTX, as well as good internalization via ASGP-R-mediated endocytosis. Therefore, the conjugates with the highest potency can be regarded as a promising therapeutic option against HCC. 相似文献
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Kachalova AV Zatsepin TS Romanova EA Stetsenko DA Gait MJ Oretskaya TS 《Nucleosides, nucleotides & nucleic acids》2000,19(10-12):1693-1707
Chemical syntheses of 2'-O-(allyloxycarbonyl)methyladenosine, 2'-O-(methoxycarbonyl)methyladenosine and 2'-O-(2,3-dibenzoyloxy)propyluridine 3'-2-cyanoethyl-N,N-diisopropyl phosphoramidite building blocks are described. These monomers were used successfully to incorporate carboxylic acid, 1,2-diol and aldehyde functionalities into synthetic oligonucleotides. 相似文献
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Fibrillarin is an evolutionarily-conserved and obligatory protein component of eukaryotic cell nucleoli involved in pre-rRNA
processing and methylation. In vertebrates the fibrillarin molecule contains two cysteine residues (Cys99 and Cys268) whose
sulfhydryl groups are able to establish intramolecular -S-S- bridges. However, the functional state of fibrillarin with reduced
or oxidized thiol groups is still practically unstudied. Besides, there are no data in the literature concerning existence
of the -S-S- fibrillarin form in human cells. To answer these questions, we used plasmids encoding native human fibrillarin
and its mutant form devoid of cysteine residues (fibrillarinC99/268S) fused with EGFP for temporary transfection of HeLa cells.
The mobile fraction localizing the enzymatically active protein molecules and the fluorescence half-recovery time characterizing
the rate of enzymatic reactions were determined by the FRAP technique using a confocal laser scanning microscope. Measurements
were carried out at 37 and 27°C. The results show that the fibrillarin pool in HeLa cells includes two protein forms, with
reduced SH groups and with oxidized SH groups forming intramolecular -S-S- bridges between Cys99 and Cys268. However, the
absence of Cys99 and Cys268 has no effect on intracellular localization of fibrillarin and its main dynamic parameters. The
human fibrillarin form without disulfide bridges is included into the mobile protein fraction and is consistent with its functionally
active state. 相似文献
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Legeza VI Grebeniuk AN Zatsepin VV 《Radiatsionnaia biologiia, radioecologiia / Rossi?skaia akademiia nauk》2011,51(1):70-75
Actions of medical radiation protection of liquidators of consequences of on Chernobyl atomic power station accident are analysed. It is shown, that during the early period of the accident medical protection of liquidators was provided by administration of radioprotectors, means of prophylaxis: of radioactive iodine incorporation and agent for preventing psychological and emotional stress. When carrying out decontamination and regenerative works, preparations which action is caused by increase of nonspecific resistance of an organism were applied. The lessons taken from the results of the Chernobyl accident, have allowed one to improve the system of medical protection and to introduce in practice new highly effective radioprotective agents. 相似文献
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Korolev S Knyazhanskaya E Anisenko A Tashlitskii V Zatsepin TS Gottikh M Agapkina J 《Nucleosides, nucleotides & nucleic acids》2011,30(7-8):651-666
Integration of the DNA copy of the genomic RNA into an infected cell genome is one of the key steps of the replication cycle of all retroviruses. It is catalyzed by the viral enzyme, integrase. We have shown that conjugates of short single-stranded oligonucleotides with eosin efficiently inhibit the catalytic activity of the HIV-1 integrase. In this article, we have found that the dependence of the integrase catalytic activity on the concentration of oligonucleotides has a bell-shaped pattern. The modulation of HIV-1 integrase activity correlated with the oligonucleotide length and was not associated with specific sequences. Moreover, a similar mode of the oligonucleotide action was found for integrase from the prototype foamy virus. This dual effect of the oligonucleotide and their conjugates with eosin might be explained by their binding with retroviral integrase in two different sites; the oligodeoxynucleotide binding in the first site results in integrase activation, whereas interactions with another one lead to inhibition of the enzyme activity. Eosin coupling to oligonucleotides did not change the mode of their action but enhanced their affinity to both binding sites. The affinity increase was found to be much more important for the site responsible for the integrase inhibition, thus explaining the high inhibitory potency of oligonucleotide-eosin conjugates. 相似文献
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T. A. Yagudin E. V. Klyatchko S. S. Zatsepin E. V. Morozkina S. V. Benevolensky O. B. Shemchukova L. P. Pozdnyakova O. N. Solopova P. G. Sveshnikov 《Applied Biochemistry and Microbiology》2016,52(4):378-383
The yeast strain Pichia pastoris, a producer of humanized F(ab’)2 fragments of rabies-blocking antibodies, has been obtained. Human chaperone BiP coexpression caused a twofold increase of the immunoglobulins secretion level. The use of Fos and Jun zippers in the composition of heavy chains facilitated the dimerization of F(ab’)2 fragments of the shared pool of secreted immunoglobulins up to 75%. 相似文献
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Zubin EM Stetsenko DA Zatsepin TS Gait MJ Oretskaya TS 《Bioorganic & medicinal chemistry》2005,13(16):4912-4920
2'-O-[2-(2,3-Diacetoxypropyl)amino-2-oxoethyl]uridine 3'-phosphoramidite was prepared and used in solid-phase synthesis to obtain oligonucleotides containing a 1,2-diol group, which may then be converted into a 2'-aldehyde group. The oligonucleotides were conjugated efficiently to various molecules by chemoselective ligation that involves an addition-elimination reaction between the 2'-aldehyde group and a suitable nucleophile, such as a hydrazine, a O-alkylhydroxylamine or an 1,2-aminothiol. The method was applied successfully to the conjugation of peptides to oligonucleotides at the 2'-position. 相似文献