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61.
Yan A. Ivanenkov Alexey E. Machulkin Anastasia S. Garanina Dmitry A. Skvortsov Anastasia A. Uspenskaya Ekaterina V. Deyneka Alexander V. Trofimenko Elena K. Beloglazkina Nikolay V. Zyk Victor E Koteliansky Dmitry S. Bezrukov Anastasia V. Aladinskaya Nataliya S. Vorobyeva Maria M. Puchinina Grigory K. Riabykh Alina A. Sofronova Alexander S. Malyshev Alexander G. Majouga 《Bioorganic & medicinal chemistry letters》2019,29(10):1246-1255
Prostate-specific membrane antigen (PSMA), also known as glutamate carboxypeptidase II (GCPII), has recently emerged as a prominent biomarker of prostate cancer (PC) and as an attractive protein trap for drug targeting. At the present time, several drugs and molecular diagnostic tools conjugated with selective PSMA ligands are actively evaluated in different preclinical and clinical trials. In the current work, we discuss design, synthesis and a preliminary biological evaluation of PSMA-specific small-molecule carrier equipped by Doxorubicin (Dox). We have introduced an unstable azo-linker between Dox and the carrier hence the designed compound does release the active substance inside cancer cells thereby providing a relatively high Dox concentration in nuclei and a relevant cytotoxic effect. In contrast, we have also synthesized a similar conjugate with a stable amide linker and it did not release the drug at all. This compound was predominantly accumulated in cytoplasm and did not cause cell death. Preliminary in vivo evaluation has showed good efficiency for the degradable conjugate against PC3-PIP(PSMA+)-containing xenograft mine. Thus, we have demonstrated that the conjugate can be used as a template to design novel analogues with improved targeting, anticancer activity and lower rate of potential side effects. 3D molecular docking study has also been performed to elucidate the underlying mechanism of binding and to further optimization of the linker area for improving the target affinity. 相似文献
62.
The assumption that the formation of pyrimidine dimers in E. coli cells, placed in a transient aqueous medium exposed to gamma-quanta, is conditioned by Cerenkov radiation laid the basis for the development of a biophysical model to explain the photoreactivation effect observed. The dependence of the effect upon gamma-radiation energy and the volume of the exposed suspension is predicted and compared with experimental data. 相似文献
63.
Irina Strazhesko Olga Tkacheva Sergey Boytsov Dariga Akasheva Ekaterina Dudinskaya Vladimir Vygodin Dmitry Skvortsov Peter Nilsson 《PloS one》2015,10(8)
Background
Chronic inflammation and oxidative stress might be considered the key mechanisms of aging. Insulin resistance (IR) is a phenomenon related to inflammatory and oxidative stress. We tested the hypothesis that IR may be associated with cellular senescence, as measured by leukocyte telomere length (LTL), and arterial stiffness (core feature of arterial aging), as measured by carotid-femoral pulse wave velocity (c-f PWV).Methods
The study group included 303 subjects, mean age 51.8 ±13.3 years, free of known cardiovascular diseases and regular drug consumption. For each patient, blood pressure was measured, blood samples were available for biochemical parameters, and LTL was analyzed by real time q PCR. C-f PWV was measured with the help of SphygmoCor. SAS 9.1 was used for statistical analysis.Results
Through multiple linear regression analysis, c-f PWV is independently and positively associated with age (p = 0.0001) and the homeostasis model assessment of insulin resistance (HOMA-IR; p = 0.0001) and independently negatively associated with LTL (p = 0.0378). HOMA-IR seems to have a stronger influence than SBP on arterial stiffness. In all subjects, age, HOMA-IR, LTL, and SBP predicted 32% of the variance in c-f PWV. LTL was inversely associated with HOMA-IR (p = 0.0001) and age (p = 0.0001). In all subjects, HOMA-IR, age, sex, and SBP predicted 16% of the variance in LTL.Conclusions
These data suggest that IR is associated with cell senescence and arterial aging and could, therefore, become the main target in preventing accelerated arterial aging, besides blood pressure control. Research in telomere biology may reveal new ways of estimating cardiovascular aging and risk. 相似文献64.
Stepanenko VF Skvortsov VG Ivannikov AI Dubov DV Tsyb AF 《Radiatsionnaia biologiia, radioecologiia / Rossi?skaia akademiia nauk》2011,51(1):168-177
The overview of the results of development, verification and application of the methods of individual retrospective physical dosimetry among population of settlements contaminated with radionuclides, which suffered from irradiation as a result of the accident in Chernobyl NPP, and among the population located in the vicinity of the Semipalatinsk nuclear test site is presented in the paper. The estimations of sensitivity of the methods of physical retrospective dosimetry are shown. The data on individual doses among population, which was irradiated as a result of accidental irradiation are presented as well. 相似文献
65.
Smirnov LD Kuznetsov IuV Proskuriakov SIa Skvortsov VG Nosko TN Dontsov AE 《Biofizika》2011,56(2):316-321
The antiradical and NO-inhibiting activities of beta-hydroxy(ethoxy) derivatives of nitrous heterocycles (3-hydroxypyridine, 5-hydroxybenzimodazole, and 6-hydroxy(alkoxy)-benzothiazole) have been studied. The antiradical activity has been studied using a homogeneous hydrophilic chemiluminescent system, and the quenching constants (Ki) have been determined. For the most reactive compound, 4-methylthiobenzimidazolyl-3-hydroxypyridine, Ki = 4.5 x 105 M(-1). The NO-inhibiting activity was estimated on a model of the endotoxin shock of experimental animals using a spin trap of nitric oxide radicals based on complexes of iron with sodium diethyldithiocarbamate. It was found that the compounds at doses of 0.25-1 mmol/kg have both the inhibitory and stimulating action on the production of nitric oxide in the liver of animals. The results obtained suggest that some derivatives of nitrous heterocycles can be used as effective antioxidant preparations. 相似文献
66.
67.
Y A Knirel I M Skvortsov A S Shashkov B A Dmitriev N K Kochetkov E S Stanislavsky G M Mashilova 《European journal of biochemistry》1985,150(3):551-557
Lipopolysaccharides were isolated from the phenol layer on aqueous phenol extraction of cells of Pseudomonas aeruginosa O11 (Lányi classification), strains 170021 and 170040. On mild acid degradation of the lipopolysaccharides, with the subsequent gel-filtration on Sephadex G-50, neutral O-specific polysaccharides made up of 6-deoxysugars alone were obtained. Two 2-acetamido-2,6-dideoxy-L-galactose (LFucNAc), 2-acetamido-2,6-dideoxy-D-glucose (DQuiNAc) and L-rhamnose (LRha) residues were found to be the components of the strain 170021 polysaccharide repeating units; those of strain 170040 contained the same monosaccharides, but, instead of 2-acetamido-2,6-dideoxy-D-glucose residue, that of 2-acetamido-2,6-dideoxy-D-galactose (DFucNAc) was present. On the basis of the 13C nuclear magnetic resonance data, methylation analysis and three successive Smith degradations the following structures were determined for the polysaccharide repeating units: strain 170021----2) LRha(alpha 1----3)LFucNAc(alpha 1----3)LFucNAc(alpha 1----3)DQuiNAc(beta 1----; strain 170040,----2)LRha(alpha 1----3)LFucNAc-(alpha 1----3)LFucNAc(alpha 1----3)DFucNAc(beta 1----; differing from one another by configuration of C-4 of 2-acetamido-2,6-dideoxy-D-hexopyranose only. 相似文献
68.
Non-linear analysis of GeneChip arrays 总被引:2,自引:1,他引:1
The application of microarray hybridization theory to Affymetrix GeneChip data has been a recent focus for data analysts. It has been shown that the hyperbolic Langmuir isotherm captures the shape of the signal response to concentration of Affymetrix GeneChips. We demonstrate that existing linear fit methods for extracting gene expression measures are not well adapted for the effect of saturation resulting from surface adsorption processes. In contrast to the most popular methods, we fit background and concentration parameters within a single global fitting routine instead of estimating the background before obtaining gene expression measures. We describe a non-linear multi-chip model of the perfect match signal that effectively allows for the separation of specific and non-specific components of the microarray signal and avoids saturation bias in the high-intensity range. Multimodel inference, incorporated within the fitting routine, allows a quantitative selection of the model that best describes the observed data. The performance of this method is evaluated on publicly available datasets, and comparisons to popular algorithms are presented. 相似文献
69.
Chikhirzhina E. V. Polyanichko A. M. Skvortsov A. N. Kostyleva E. I. Houssier C. Vorob'ev V. I. 《Molecular Biology》2002,36(3):412-418
The method of circular dichroism (CD) was used to compare DNA behavior during its interaction with linker histone H1 and with nonhistone chromosomal protein HMG1 at different ionic strength and at different protein content in the system. The role of the negatively charged C-terminal segment of HMG1 was analyzed using recombinant protein HMG1-(A+B), which lacks the C-terminal amino acid sequence. The -type CD spectra were common for DNA interaction with histone H1, but no spectra of this type were observed in HMG1–DNA systems even at high ionic strength. The CD spectrum of the truncated recombinant protein at high salt concentration somewhat resembled the +-type spectrum. Two very intense positive bands were located near 215 nm and near 272 nm, and the whole CD spectrum was positive. The role of the C-terminal part of HMG1 in the formation of ordered DNA–protein complexes is discussed. 相似文献
70.
Inhibition of histone deacetylase activity enhances Fas receptor-mediated apoptosis in leukemic lymphoblasts 总被引:4,自引:0,他引:4
Bernhard D Skvortsov S Tinhofer I Hübl H Greil R Csordas A Kofler R 《Cell death and differentiation》2001,8(10):1014-1021
We recently reported that butyrate, an inhibitor of histone deacetylases, is capable of inducing Fas-independent apoptosis in the acute lymphoblastic leukemia cell line CCRF-CEM. Here we demonstrate that butyrate enhances Fas-induced apoptosis in this cell line. The application of different histone deacetylase inhibitors revealed that tetra-acetylated histone H4 is associated with the amplifying effect of butyrate on Fas-induced cell death. FasL, Fas, FADD, RIP, caspase-8, caspase-3, Bid, FLIP(S+L), FLASH and FAP-1, proteins known to act within the Fas-apoptosis cascade, showed no changes in their expression levels in cells treated with butyrate compared with untreated cells. Analyses of Fas-oligomerization and Western blotting as well as enzyme activity assays of caspase-2, caspase-3 and caspase-8 suggest that butyrate enhances Fas-induced apoptosis downstream of Fas but upstream of caspase-8 activation. In immunoprecipitation experiments a 37 kD butyrate-regulated protein was detected which specifically interacts with caspase-8. 相似文献