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V A Nikolaev

Publications and source records attributed to V A Nikolaev.

16 recordsLinked to original sources
PubMed2006

The 2-oxocyclobutanecarboxylic acid keto-enol system in aqueous solution: a remarkable acid-strengthening effect of the cyclobutane ring.

Flash photolysis of 2-diazocyclopentane-1,3-dione in aqueous solution produced 2-oxocyclobutylideneketene, which underwent hydration to the enol of 2-oxocyclobutanecarboxylic acid; the enol then isomerized to the keto form of this acid. Rates of the ketene and enol reactions were measured in acid, base, and buffer solutions across the acidity range [H+] = 10(-1)-10(-13) M, and analysis of these data, together with rates of enolization of the keto form of 2-oxocyclobutanecarboxylic acid determined by bromine scavenging, gave keto-enol equilibrium constants as well as acidity constants of the keto and enol forms. The keto-enol equilibrum constants proved to be 2 orders of magnitude less than those reported previously for the next higher homolog, 2-oxocyclopentanecarboxylic acid, reflecting the difficulty of inserting a carbon-carbon double bond into a small, strained carbocyclic ring. The acidity constant of the enol group of 2-oxocyclobutanecarboxylate ion, on the other hand, is greater, by 4 orders of magnitude, than that of the corresponding enol in the cyclopentyl system. This remarkable increase in acidity with diminishing ring size is consistent with the enhanced s character of the orbitals used to make the exocyclic bonds of the smaller cyclobutane ring.

Journal Article↗
PubMed2003

The 2-oxocyclohexanecarboxylic acid keto-enol system in aqueous solution.

Flash photolysis of 2-diazocycloheptane-1,3-dione or 2,2-dimethyl-5,6,7,8-tetrahydrobenzo-4H-1,3-dioxin-4-one in aqueous solution produced 2-oxocyclohexylideneketene, which underwent hydration to the enol of 2-oxocyclohexanecarboxylic acid, and the enol then isomerized to the keto form of the acid. Isomerization of the enol to keto forms was also observed using solid enol, a substance heretofore commonly believed to be the keto acid. Rates of ketonization were measured in perchloric acid, sodium hydroxide, and buffer solutions, and a ketonization rate profile was constructed. Rates of enolization of the keto acid were also measured using bromine to scavenge the enol as it formed. Rates of enolization and ketonization were then combined to provide the keto-enol equilibrium constant pK(E) = 1.27. This and some of the other results obtained are different from the corresponding quantities for the 2-oxocyclopentanecarboxylic acid keto-enol system. These differences are discussed.

Journal Article↗
PubMed2001

Ketene reactions with the aminoxyl radical tempo: preparative, kinetic, and theoretical studies.

Tetramethylpiperidinyloxy (TEMPO, TO*) reacts with ketenes RR(1)C=C=O generated by either Wolff rearrangement or by dehydrochlorination of acyl chlorides to give products resulting from addition of one TEMPO radical to the carbonyl carbon and a second to the resulting radical. Reactions of phenylvinylketenes 4b and 4f, phenylalkynylketene 4c, and the dienylketene AcOCMe=CHCH=CHCMe=C=O (11) occur with allylic or propargylic rearrangement. Even quite reactive ketenes were generated as rather long-lived species by photochemical Wolff rearrangement in isooctane solution, characterized by IR and UV, and used for kinetic studies. The rate constants of TEMPO addition to eight different ketenes have been measured and give a qualitative correlation of log k(2)(TEMPO) = 1.10 log k(H(2)O) -3.79 with the rate constants for hydration of the same ketenes. Calculations at the B3LYP/6-311G//B3LYP/6-311G level are used to elucidate the ring opening of substituted cyclobutenones leading to vinylketenes and of 2,4-cyclohexadienone (17) forming 1,3,5-hexatrien-1-one (18).

Journal Article↗
PubMed1996

Design of sequence-specific DNA binding ligands that use a two-stranded peptide motif for DNA sequence recognition.

The design and DNA binding activity of beta-structure-forming peptides and netropsin-peptide conjugates are reported. It is found that a pair of peptides-S,S'-bis(Lys-Gly-Val-Cys-Val-NH-NH-Dns)-bridged by an S-S bond binds at least 10 times more strongly to poly(dG).poly(dC) than to poly(dA).poly(dT). This peptide can also discriminate between 5'-GpG-3' and 5'-GpC-3' steps in the DNA minor groove. Based on these observations, new synthetic ligands, bis-netropsins, were constructed in which two netropsin-like fragments were attached by means of short linkers to a pair of peptides-Gly-Cys-Gly- or Val-Cys-Val-bridged by S-S bonds. These compounds possess a composite binding specificity: the peptide chains recognize 5'-GpG-3' steps on DNA, whereas the netropsin-like fragments bind preferentially to runs of 4 AT base pairs. Our data indicate that combining the AT-base-pair specific properties of the netropsin-type structure with the 5'-GpG-3'-specific properties of certain oligopeptides offers a new approach to the synthesis of ligands capable of recognizing mixed sequences of AT- and GC-base pairs in the DNA minor groove. These compounds are potential models for DNA-binding domains in proteins which specifically recognize base pair sequences in the minor groove of DNA.

Aminoglycosides↗
PubMedDate not supplied

[Ligands with specific affinity to a specific sequence of DNA base pairs. XI. The synthesis and binding to DNA of bis-netropsins with the C-ends of their netropsin fragments tethered by tetra- or pentamethylene linkers].

Bis-Netropsins with the C-ends of their netropsin fragments tethered via tetra- or pentamethylene linkers and with Gly or L-Lys-Gly residues on their N-ends were synthesized. The footprinting technique was used to study the specificity of bis-netropsin binding to the specially constructed DNA fragments containing various clusters of A.T pairs. It was found that the linker length affects the binding of bis-netropsins, with the tetramethylene linker providing better protection than the pentamethylene linker. It was shown that the newly synthesized bis-netropsins bind tighter to the 5'-A4T(4)-3' sequence, whereas the bis-netropsin with a linker between the netropsin N-ends binds better to 5'-T4A(4)-3' sequences. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2002, vol. 28, no. 6; see also http://www.maik.ru.

Base Pairing↗
PubMedDate not supplied

[Specific DNA cleavage by an analog of netropsin containing a copper(II) chelating peptide Gly-Gly-His].

Experimental data are reported on DNA-cleaving activity of the synthetic netropsin analogs consisting of the two N-propylpyrrole carboxamide units linked covalently through two or three glycine residues to a copper-chelating tripeptide glycyl-glycyl-L-histidine. Incubation of DNA restriction fragment and netropsin analog in the presence of ascorbate, hydrogen peroxide and Cu2+ ions resulted in selective cleavage of the DNA at or near the preferred sites for binding of netropsin analog. A similar cleavage pattern is observed after X-ray irradiation of DNA complexes with netropsin analogs tethered with Cu2+ ions. The cleavage patterns are found to be dependent on the length of the connecting chain between the histidine-containing tripeptide and netropsin analog. The netropsin analog containing three glycine residues in the connecting chain, but not the analog with a shorter linker chain, can generate an intense cleavage of one of the two polynucleotide chains at a position corresponding to the presumed binding site for the dimeric ligand species. More than 50% of the total DNA can be cleaved at this position after X-ray irradiation. From analysis of the nucleotide sequences surrounding the preferred cleavage site on several DNA fragments we found that the consensus is 5'-TTTTNCA*AAA-3', where N is an arbitrary nucleotide. The Cu(2+)-mediated cleavage of DNA occurs at the second adenine (indicated by an asterisk) from the 5'-end of the sequence. The greatest cleavage activity is observed when the molar ratio of Cu2+ to the netropsin analog is equal to 0.5. Evidently, the Cu(2+)-ligated and unligated oligopeptide species interacts with each other to form a heterodimer bound to DNA at the cleavage site. To test the validity of this model we have studied the binding of unligated netropsin analog and netropsin analog complexed with Cu2+ ion to a self-complementary oligonucleotide 5'-GCGTTTTGCAAAACGC-3'. It is found that binding of Cu(2+)-ligated netropsin analog to the DNA oligomer preincubated with unligated form of the oligopeptide is a cooperative process for which interactions between the two bound ligands are responsible. The cooperativity parameter is estimated to be on the order of factor 6. Finally, a model is proposed in which a heterodimer stabilized by interligand beta-sheet binds in the minor DNA groove.

Amino Acid Sequence↗
PubMedDate not supplied

[Interaction of a cysteine-containing peptide with DNA].

Cystine peptide dimer (Lys-Gly-Val-Cys-Val-N2H2Dns)2 with S-S bridge was synthesized and its interactions with DNA and synthetic polynucleotides have been studied by optical spectroscopy methods. By recording fluorescent titration curves we have shown that the affinity of the peptide to different synthetic polynucleotides decreases in the order: poly(dG).poly(dC) greater than poly(dA).poly(dT) greater than poly(dGC).poly(dGC). The stability of complexes to increasing concentrations of NaCl diminishes in the same order. The association constant is about 20-fold greater for peptide binding to poly(dG).poly(dC) than to poly(dA).poly(dT). By using circular dichroism and fluorescence measurements we have shown that the peptide competes for the binding sites on DNA with two minor-groove binding antibiotics--distamycin A and sybiromycin. These results have suggested that the peptide also binds in the DNA minor groove. Investigation of the interactions between such peptides and DNA may be useful for constructing ligands with combined specificity to DNA.

Amino Acid Sequence↗
PubMedDate not supplied

[Synthetic DNA-bindings ligands containing reaction centers specific for AT- and GC-pairs in DNA].

In the present communication design, synthesis and DNA binding activities of three bis-netropsins and two netropsin analogs containing two N-propylpyrrolecarboxamide fragments linked covalently to peptides Gly-Gly-(analog I) and Val-Val-Val-Gly-Gly-(analog II) are reported. Each bis-netropsin consists of two netropsin-like fragments attached to peptides -Gly-Cys-Gly-NH2 (compound IIIa), H-Gly-Cys-Gly-Gly-Gly-(compound IV) or Gly-Cys-Sar-NH2 (compound IIIb) which are linked symmetrically via S-S bonds. Physico-chemical studies show that each bis-netropsin carries 6 AT-specific reaction centers and covers approximately 10 base pairs upon binding to poly(dA).poly(dT). This indicates that two netropsin-like fragments of the bis-netropsin molecule are implicated in specific interaction with DNA base pairs. The peptide fragments of bis-netropsins IIIa and IV form small beta-sheets containing two-GC-specific reaction centers. The DNase I cleavage patterns of bis-netropsin-DNA complexes visualized by high resolution gel electrophoresis show that the preferred binding sites for bis-netropsins IIIa and IV are identical and contain two runs of three or more AT pairs separated by two GC pairs. Specificity determinants of netropsin analog II binding in the beta-associated dimeric form are identical to those of bis-netropsin IIIa thereby indicating that there is a similarity in the structure of complexes formed by these ligands with DNA. In the monomeric form analog II exhibits binding specificity identical to that of analog I. Replacement of C-terminal glycine residues by sarcosines in the peptide fragments of bis-netropsin IIIa leads to a decrease in the affinity of ligand for DNA.

Base Composition↗
PubMedDate not supplied

[Attachment of trivaline changes the specificity of binding of netropsin analogs with DNA].

In the present communication, synthesis and DNA binding activities of three analogs of the antibiotic netropsin are reported. Each analog contains two N-propylpyrrolecarboxamide units linked covalently to either Dns-Gly-Val-Val-Val-Gly-Gly- (I), Val-Val-Val-Gly-Gly (II) or Gly-Gly (III). It is shown that analogs I and II can self-associate in aqueous solution and methanol as revealed from the fact that UV absorbance and circular dichroism spectra obtained for these analogs are concentration-dependent. By contrast, analogs III exists as a monomer, even at concentration levels of the order of 1.10(-3) M. Determination of the apparent sizes of intramolecular aggregates by gel-filtration shows that analog I in aqueous solution at concentration levels of the order of 1.10(-3) M forms a series of aggregates containing from 2 to 12 monomers. Analog II exhibits a lower tendency to form intermolecular aggregates as compared with that of analog I. Dimerization constants are determined for analogs I and II in aqueous solution and methanol. The binding of N-propylpyrrolecarboxamide units and peptide fragments of analog I to DNA can be independently monitored by circular dichroism and fluorescence methods. If self-associated species of analog I (or II) are present in solution, the ligand exhibits a markedly different order of base pair sequence preferencies as compared with that of analog III. The results obtained are consistent with the inference that analogs I and II in a beta-associated form recognizes base pair sequences containing two runs of 3 AT pairs separated by two GC pairs.

Base Sequence↗
PubMedDate not supplied

[A synthetic zinc chelating peptide competes for DNA binding sites with antibiotics, adsorbed in a minor DNA groove].

Effects of sibiromicyn, distamicyn A and its analogs on binding to DNA and to poly(dA).poly(dT) are reported for a 23-amino acid synthetic zinc-binding peptide, a part of the DNA-binding domain of the transcriptional activator GAL-4. Circular dichroism and fluorometry have shown that the synthetic peptide and two distamicyn A analogs compete for binding sites on DNA and on poly(dA).poly(dT). Antibiotic sibiromycin which forms a covalent bond with a guanine 2-amino group in the minor DNA groove can displace the peptide from a 19 bp self-complementary oligonucleotide serving as a specific target site for Gal-4 protein. The peptide is shown to bind to a glucosylated phage T2 DNA, but its affinity to T2 DNA is weaker than to calf thymus DNA under the same conditions. A method to estimate binding constant and size of the binding site for the synthetic peptide and poly(dA).poly(dT) is proposed based on the binding isotherms of distamycin analogs in the absence and in the presence of the peptide. Using isotherms of binding to poly(dA).poly(dT) for two distamycin analogs with binding constants differing 60-fold, the binding constant of the peptide in the presence of 0.1 M NaCl is estimated as 1.4.10(7)-1.8.10(7) M-1.

Anti-Bacterial Agents↗
PubMedDate not supplied

[The adaptive reaction of the blood lymphocytes in persons subjected to chronic radiation exposure at low doses].

The changes in the PHA-stimulated human blood lymphocytes of the peoples from Moscow and from polluted after Chernobyl disaster Bryansk region were studied. The decrease in lymphocyte mitotic index in residents from polluted regions was revealed. Moscow population was not distinguished from Bryansk region population by the frequency of cells with micronuclei. There was also no difference in frequency of micronuclei after 1 Gy irradiation of the these populations. The adaptive response (irradiation with a dose of 0.05 Gy followed by 1.0 Gy irradiation 5 hours later) was studied. The decrease in the number of individuals with adaptive response and appearance of the individuals with increased radiosensitivity in the population of polluted regions were observed. There was no such subpopulation among the Moscow residents. So, firstly, low dose chronic irradiation is not an adaptive factor; secondly, the determination of adaptive response can be methodological procedure for the revealing the changes which were induced by low dose chronic irradiation (accompanied by other environment agents).

Adaptation, Physiological↗
PubMedDate not supplied

[Ligands with affinity to specific sequences of DNA base pairs. X. Synthesis and binding of netropsin analogs, containing a chelating copper ion peptide, with DNA].

An analogue of netropsin has been synthesized consisting of two N-propylpyrrolcarboxamide units linked covalently to a copper-chelating tripeptide Gly-Gly-L-His by means of two and three glycine residues. Binding to DNA and synthetic polynucleotides of netropsin analogue containing three glycine residues between Gly-Gly-L-His tripeptide and the N-end of netropsin analogue (His-Nt) has been studied. It is shown that this netropsin analogue chelates a copper ion with 1:1 stoichiometry, similar to a free Gly-Gly-L-His peptide. It is found that this netropsin analogue occupies 3 to 4 base pairs upon binding to poly(dA).poly(dT) and poly[d(AT)].poly[d(AT)] polymers, irrespective of whether it binds in Cu(2+)-ligated or unligated forms. Binding constants and binding site sizes have been calculated for netropsin analogue complexes with DNA, poly(dA).poly(dT) and poly[d(AT)].poly[d(AT)] polymers at the [Cu2+]/[His-Nt] ratio equal to 0 and 1.0. In the three-component system including His-Nt and Cu(2+)-His-Nt, cooperative effects are recognized which can be explained by heterodimer generation on interaction of His-Nt and Cu(2+)-His-Nt at adjacent binding sites.

Amino Acid Sequence↗