Tag Archives: biological activity
Рantoea agglomerans lipopolysaccharides: structure, functional and biological activity
L. D. Varbanets, Т. V. Bulyhina, L. А. Pasichnyk, N. V. Zhytkevich
Zabolotny Institute of Microbiology and Virology,
National Academy of Sciences of Ukraine, Kyiv;
e-mail: varbanets_imv@ukr.net
Received: 02 September 2018; Accepted: 13 December 2018
This review analyzed literature data, as well as our own research on lipopolysaccharides (LPS) of gram-negative bacteria, focusing mainly on Pantoea agglomerans, a member of the Enterobacteriaceae family. The unique structures of O-specific polysaccharide chains of LPS from Pantoea agglomerans represented by both linear and branched tetra- and pentasaccharide repeating units were described for the first time. The heterogeneity of the LPS molecule itself and the presence of several LPS in the bacterial cell, which differ in the structure of lipids A, O-specific polysaccharide chains, serological activity, as well as endotoxic properties, such as toxicity and pyrogenicity, were shown. Such heterogeneity represents one of the mechanisms of LPS multifunctionality. Based on the antigenicity of LPS, serotyping of P. agglomerans strains and their assignment to 10 serogroups were carried out for the first time. The high immunomodulatory activity of P. agglomerans LPS suggests the possibility to use their oligosaccharide fragments in the development of conjugated vaccines against diseases caused by gram-negative bacteria.
Energetic, conformational and electron density topological properties of 2′,3′-didehydro-2′,3′-dideoxythymidine: a quantum chemical study
A. G. Ponomareva, Ye. P. Yurenko, R. O. Zhurakivsky
Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv;
e-mail: a.g.ponomareva@gmail.com; yevgen.yurenko@gmail.com; roman@zhr.org.ua
Comprehensive conformational analysis of 2′,3′-didehydro-2′,3′-dideoxythymidine (d4T), also known as anti-AIDS drug stavudine, has been performed for the first time at the MP2/6-311++G(d,p)//DFT B3LYP/6-31++G(d,p) level of the theory. It was established that d4T energy landscape contained 19 local minima, which corresponded to stable conformers. Eight types of specific intramolecular interactions, which govern the d4T conformational properties, were identified, namely: O5′H∙∙∙O2, C1′H′∙∙∙O2, C6H∙∙∙O5′, C6H∙∙∙O4′, C5′H1′∙∙∙O2, C5′H2′∙∙∙O2, C6H∙∙∙H1′C5′, C2′∙∙∙O2. The obtained results confirm the actual point of view that d4T biological activity is, most likely, connected with termination of the DNA chain synthesis in the 5′-3′ direction. Thus, d4T competes with canonical thymidine in binding an active site of HIV-1 reverse transcriptase.
Validation of biological activity testing procedure of recombinant human interleukin-7
T. N. Lutsenko1,2, M. V. Kovalenko3, O. Yu. Galkin2
1LLC “UA PRO-PHARMA”, Kyiv;
2National Technical University of Ukraine “Igor Sikorsky Kyiv Polytechnic Institute”;
3Institute of Molecular Biology and Genetics of the National
Academy of Sciences of Ukraine, Kyiv;
e-mail: tanywalytsenko@gmail.com
Validation procedure for method of monitoring the biological activity of reсombinant human interleukin-7 has been developed and conducted according to the requirements of national and international recommendations. This method is based on the ability of recombinant human interleukin-7 to induce proliferation of T lymphocytes. It has been shown that to control the biological activity of recombinant human interleukin-7 peripheral blood mononuclear cells (PBMCs) derived from blood or cell lines can be used. Validation characteristics that should be determined depend on the method, type of product or object test/measurement and biological test systems used in research. The validation procedure for the method of control of biological activity of recombinant human interleukin-7 in peripheral blood mononuclear cells showed satisfactory results on all parameters tested such as specificity, accuracy, precision and linearity.
Conformational capacity of 2′,3′-didehydro-2′,3′-dideoxyadenosine as a key to understanding its biological activity: results of quantum chemical modelling
A. G. Ponomareva1, Ye. P. Yurenko1, R. O. Zhurakivsky1, D. M. Hovorun1,2
1Institute of Molecular Biology and Genetics, National Academy
of Sciences of Ukraine, Kyiv;
e-mail: yevgen.yurenko@gmail.com;
2Institute of High Technologies, Taras Shevchenko Kyiv
National University, Ukraine
Comprehensive conformational analysis of the biologically active nucleoside 2′,3′-didehydro-2′,3′-dideoxyadenosine (d4A) has been performed at the MP2/6-311++G(d,p)//DFT B3LYP/6-31G(d,p) level of theory. The energetic, geometrical and polar characteristics of twenty one d4A conformers as well as their conformational equilibrium were investigated. The electron density topological analysis allowed us to establish that the d4A molecule is stabilized by eight types of intramolecular interactions: O5′H…N3, O5′H…C8, C8H…O5′, C2′H…N3, C5′H1…N3, C5′H2…N3 та C8H…H1/2C5′. The obtained results of conformational analysis lead us to think that d4A may be a terminator of the DNA chain sythesis in the 5′-3′ direction. Thus it can be inferred that d4A competes with canonical 2′-deoxyadenosine in binding an active site of the corresponding enzyme.
Complete conformational family of 2′,3′-didehydro-2′,3′-dideoxyguanosine: quantum chemical and electron density topological study
A. G. Ponomareva1, Ye. P. Yurenko1,2,3, R. O. Zhurakivsky1,2, D. M. Hovorun1,2,3
1Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv;
e-mail: yevgen.yurenko@gmail.com;
2Research and educational center “State key laboratory of molecular and cell biology”, Kyiv, Ukraine;
3Taras Shevchenko Kyiv National University, Institute of High Technologies, Ukraine;
e-mail: dhovorun@imbg.org.ua
Comprehensive conformational analysis of the biologically active nucleoside 2′,3′-didehydro-2′,3′-dideoxyaguanosine (d4G) has been performed at the MP2/6-311++G(d,p)//DFT B3LYP/6-31G(d,p) level of theory. The energetic, geometrical and polar characteristics of twenty d4G conformers as well as their conformational equilibrium were investigated. The electron density topological analysis allowed us to establish that the d4G molecule is stabilized by nine types of intramolecular interactions: O5′H…N3, O5′H…C8, C8H…O5′, C2′H…N3, C5′H1…N3, C5′H2…N3, C8H…H1C5′, С8Н…Н2′С5′ and N2H1…O5′. The obtained results of conformational analysis permit us to think that d4G may be a terminator of the DNA chain synthesis in the 5′-3′ direction. Thus it can be inferred that d4G competes with canonical 2′-deoxyaguanosine in binding an active site of the corresponding enzyme.