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1.
Bioorg Khim ; 40(5): 578-87, 2014.
Article in Russian | MEDLINE | ID: mdl-25895353

ABSTRACT

By alkylation of uracil, thymine, cytosine, adenine, 6-chloropurine, and 2-amino-6-chloropurine with 5-chloro-1-(4-halogenophenyl)-1-pentanones novel derivatives of nucleic bases were obtained, their physicochemical properties were studied. The influence of synthesized compounds on HIV-1 integrase was investigated.


Subject(s)
Enzyme Inhibitors/chemistry , HIV Infections/drug therapy , HIV Integrase/chemistry , Structure-Activity Relationship , Adenine/chemistry , Alkylation , Cytosine/chemistry , Enzyme Inhibitors/pharmacology , HIV/drug effects , HIV/enzymology , HIV Infections/enzymology , HIV Infections/virology , HIV Integrase/metabolism , Humans , Purines/chemistry , Thymine/chemistry , Uracil/chemistry
2.
Bioorg Khim ; 36(4): 514-25, 2010.
Article in Russian | MEDLINE | ID: mdl-20823920

ABSTRACT

Novel polymethylene derivatives of nucleic bases containing a phenylketo function in the omega-position of hydrocarbon chain were synthesized by alkylation of uracil, thymine, cytosine, hypoxantine, adenine, and N(2)-isobutyrylguanine with omega-chloro-1 -phenylalkan-1-ones, their physicochemical properties were studied.


Subject(s)
Purines/chemistry , Purines/chemical synthesis , Pyrimidines/chemistry , Pyrimidines/chemical synthesis
3.
Mol Biol (Mosk) ; 44(6): 1045-53, 2010.
Article in Russian | MEDLINE | ID: mdl-21290826

ABSTRACT

NS3 protein of hepatitis C virus plays the key role in the virus functioning. It possesses three enzymatic activities, namely protease activity, associated with N-terminal domain of the protein, and helicase/NTPase activities specific for C-terminal domain. Here, the effect of some polimethylenic derivatives of the nucleic bases on helicase and ATPase enzyme activities has been studied. Several of compounds tested displayed inhibitory activity towards NS3 helicase. However, most compounds demonstrated strong activating effect on ATPase activity of the enzyme as well as several other ATPases. The ATPase activating mechanism was not described earlier. The activation potency of the compounds depended on substrate/activator concentration ratio, and was maximal at the 1000:1. The activation mechanism scheme that allows us to explain phenomena observed is proposed.


Subject(s)
Hepacivirus/enzymology , Nucleotides/metabolism , Nucleotides/pharmacology , Polyamines/metabolism , Polyamines/pharmacology , Viral Nonstructural Proteins/agonists , Viral Nonstructural Proteins/antagonists & inhibitors , Adenosine Triphosphatases/metabolism , Enzyme Activation , Humans , Nucleotides/chemistry , Polyamines/chemistry , RNA Helicases/antagonists & inhibitors , RNA Helicases/metabolism , Viral Nonstructural Proteins/metabolism
4.
Bioorg Khim ; 35(1): 84-94, 2009.
Article in Russian | MEDLINE | ID: mdl-19377526

ABSTRACT

New polymethylene derivatives of nucleic bases with a beta-diketo function in the omega-position were obtained by alkylation of uracil, thymine, cytosine, hypoxanthine, adenine, and N(2)-isobutyryl guanine with 2-omega-chloroal-kanoyl)cyclohexanones. The physical and chemical characteristics of the compounds synthesized and their effect on the K562 and HCT116 tumor cell lines were studied.


Subject(s)
Antineoplastic Agents/pharmacology , Cell Proliferation/drug effects , Purines/pharmacology , Pyrimidines/pharmacology , Alkylation , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Survival/drug effects , Cytosine/pharmacology , Doxorubicin/pharmacology , Drug Interactions , Drug Resistance, Neoplasm , Drug Screening Assays, Antitumor , Humans , Hypoxanthine/pharmacology , Purines/chemistry , Pyrimidines/chemistry , Structure-Activity Relationship , Thymine/pharmacology , Uracil/pharmacology
5.
Bioorg Khim ; 34(1): 75-82, 2008.
Article in Russian | MEDLINE | ID: mdl-18365741

ABSTRACT

New polymethylene derivatives of nucleic bases with beta-diketo function in omega-position were prepared by alkylation of uracil, thymine, and cytosine. Their physicochemical properties and effect on the E. coli uridine phosphorylase were studied.


Subject(s)
Escherichia coli/enzymology , Nucleic Acids/chemistry , Pyrimidines/chemistry , Uridine Phosphorylase/antagonists & inhibitors , Nucleic Acids/chemical synthesis , Pyrimidines/chemical synthesis , Uridine Phosphorylase/chemistry
6.
Bioorg Khim ; 31(6): 609-15, 2005.
Article in Russian | MEDLINE | ID: mdl-16363133

ABSTRACT

New polymethylene derivatives of nucleic bases containing a keto function in the omega-position were synthesized by alkylation of nucleic bases with 2-(3-chloropropyl)-2-phenyl-1,3-dioxolane and the subsequent deblocking of the keto group; their physicochemical properties were studied. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2005, vol. 31, no. 6; see also http://www.maik.ru.


Subject(s)
Butyrophenones/chemistry , Nucleosides/chemistry , Purines/chemistry , Pyrimidines/chemistry , Butyrophenones/chemical synthesis , Purines/chemical synthesis , Pyrimidines/chemical synthesis
7.
Bioorg Khim ; 30(5): 487-92, 2004.
Article in Russian | MEDLINE | ID: mdl-15562969

ABSTRACT

New polymethylene derivatives of nucleic bases containing a beta-dioxo function at the omega-position were synthesized by alkylation of uracil, thymine, and cytosine with 1-(7-chloroheptanoyl)cyclohexan-2-one, and their physicochemical properties were studied. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 5; see also http: // www.maik.ru.


Subject(s)
Biochemistry/methods , Methane/analogs & derivatives , Nucleosides/chemistry , Pyrimidines/chemistry , Alkylation , Cytosine/chemistry , Hydrocarbons , Methane/chemistry , Thymine/chemistry , Uracil/chemistry
8.
Bioorg Khim ; 30(4): 441-5, 2004.
Article in Russian | MEDLINE | ID: mdl-15469020

ABSTRACT

A five-step synthesis of alpha-methylspermidine (1,8-diamino-5-azanonane), the first polyamine analogue preventing pathological consequences of spermidine depletion in transgenic rats overproducing spermine/spermidine N'-acetyltransferase, from ethyl 3-aminobutyrate was achieved in a high overall yield.


Subject(s)
Spermidine/analogs & derivatives , Spermidine/chemical synthesis , Animals , Animals, Genetically Modified , Magnetic Resonance Spectroscopy/methods , Rats , Spermidine/chemistry
11.
Mol Biol (Mosk) ; 14(5): 1159-72, 1980.
Article in Russian | MEDLINE | ID: mdl-7421822

ABSTRACT

The temperature dependence of CD spectra of ApA, its (2'--5')-isomer, and a number of free conformational analogues, in which the ribose ring was replaced by acyclic hydroxyalkyl substituents, has been studied. The thermodynamic parameters of conformational equilibrium were determined. The role of separate functional groups and parts of DNP molecules in the organization and stabilization of the close state as well as the role of water in the stabilization of the one stranded helix of RNA is discussed.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Dinucleoside Phosphates , Chemical Phenomena , Chemistry , Circular Dichroism , Isomerism , Molecular Conformation , Thermodynamics
12.
Biofizika ; 25(4): 745-59, 1980.
Article in Russian | MEDLINE | ID: mdl-7417559

ABSTRACT

The strategy of quantitative study of conformational situation in aqueous solutions of dinucleoside phosphates (DNP) has been proposed. It includes the following steps: (1) conformational calculation of stacking conformers (SC) of DNP; (2) measurement of thermodynamic parameters of conformational equililbrium; (3) determination of extensive parameters of stacking state (SS) on the basis of experimental data and thermodynamic parameters; (4) computation of extensive parameters of SC on the basis of the calculated geometry of SC and theoretical concepts of experimental method; (5) comparison of experimental parameters of SS with the calculated ones of SC to establish the SC participating in the equilibrium as well as its relative weights. This strategy was exemplified by ApA, ApC, CpA and CpC. The chemical shifts, spin-spin coupling constants and spin-lattice relaxation rates of DNP protons were used. The predominant SC was found to be related to Pba type with a large twirl angle (45-54 degrees) and almost parallel base planes. For all DNP the presence in equilibrium of left-handed forms was typical. These were Mab forms for ApA, Mbb forms for CpC and CpA, Mbb and Mab forms for ApC. About 10% of SS of ApA and CpA were presented by SC with trans-conformation of C(4')-C(5') bond of oN-part. The SC with C(3')-endo, C(3')-endo combination of ribose conformations were basic for ApA, ApC and CpA, and the only possible for CpC. In case of ApA, ApC and CpA the conformers with C(3')-endo, C(2')-endo sugar combination were presented.


Subject(s)
Nucleotides , Chemical Phenomena , Chemistry , Magnetic Resonance Spectroscopy , Models, Chemical , Molecular Conformation , Solutions , Thermodynamics , Water
13.
Mol Biol (Mosk) ; 12(1): 233-9, 1978.
Article in Russian | MEDLINE | ID: mdl-634284

ABSTRACT

The dinucleoside phosphates analogues APpSU, SUPpA and UPpSU have been synthesised by direct thionation of DNP analogues, containing cytosine. The structure of compounds prepared was proved by UV- and PMR-spectra. The CD spectra of the DNP analogues were examined. It has been demonstrated that the "induced" dichroism contribution in the Cotton-effect of DNP was substantial in the case of stacking conformations and negligible for unstacking conformations.


Subject(s)
Nucleotides , Chemical Phenomena , Chemistry , Circular Dichroism , Molecular Conformation , Nucleotides/chemical synthesis , Temperature , Thiouracil
14.
Mol Biol (Mosk) ; 10(5): 1111-5, 1976.
Article in Russian | MEDLINE | ID: mdl-1053073

ABSTRACT

The dependence of the NMR spectra of adenosine 5'-phosphate and phosphates of 9-(2'-hydroxyethyl)-, 9-(3'-hydroxypropyl)- and 9-(4'-hydroxybutyl)adenines on temperature and concentration has been investigated in aqueous solutions.


Subject(s)
Adenine Nucleotides , Adenosine Monophosphate , Magnetic Resonance Spectroscopy , Structure-Activity Relationship
15.
Mol Biol (Mosk) ; 10(2): 367-77, 1976.
Article in Russian | MEDLINE | ID: mdl-7746

ABSTRACT

Circular dichroism spectra of 11 analogues of the dinucleoside phosphate containing achiral 3'-terminal monomers have been measured at several pH values, various temperatures and various concentrations of ethanol. The conformation of analogues studied has been shown to by very similar to that of natural compounds. Comparison of the results obtained with the circular dichroism spectra of the corresponding natural compounds indicates that Cotton effect arises from monomeric circular dichroism, at least in main features. The exciton interaction is relatively small.


Subject(s)
Nucleosides , Chemical Phenomena , Chemistry , Circular Dichroism , Hydrogen-Ion Concentration
17.
Mol Biol (Mosk) ; 9(1): 121-5, 1975.
Article in Russian | MEDLINE | ID: mdl-1219366

ABSTRACT

On the basis of the application of transition-state theory to enzymatic catalysis a novel approach to the synthesis of inhibitors of enzymes involving conformational rigid substrate has been proposed. It is predicted that the substrates which resemble the natural species in the structure of functional groups, but posses conformational flexibility, will be bound to the enzyme more tightly and converted more slowly than the natural substrate.


Subject(s)
Enzyme Inhibitors/chemical synthesis , Binding Sites , Molecular Conformation , Protein Binding
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