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S N Mikhaĭlov

Publications and source records attributed to S N Mikhaĭlov.

At least 19 recordsLinked to original sources
PubMed2000

[Periodate oxidation in chemistry of nucleic acid. Dialdehyde derivatives of nucleosides, nucleotides, and oligonucleotides].

The employment of periodate oxidation in the chemistry of nucleic acids and their components is reviewed. The reaction mechanism, structural requirements to substrates, and synthesis of dialdehyde derivatives of nucleosides, nucleotides, and oligonucleotides are discussed in the first part. The second part involves chemical, physicochemical, and biological properties of the dialdehyde derivatives, as well as their use for the affinity modifications of proteins.

Aldehydes↗
PubMed1998

[Acyclic nucleotide analogues based on phosphonic acids].

The synthesis of novel nucleotide analogues on the basis of ethylphosphonic acid was described. A rigid structural element, an amide or a double bond, was characteristics of the compounds synthesized. The antiviral and cytotoxic activities of these compounds were studied in cell cultures.

Amides↗
PubMed1995

[Substrate properties of dioxolane analogs of 3'-deoxythymidine-5'-triphosphate in DNA synthesis reactions, catalyzed by various DNA polymerases].

The substrate properties of 3'-deoxythymidine 5'-triphosphate analogs prepared on the basis of 2,4-disubstituted 1,3-dioxolanes were investigated in reactions of the DNA synthesis catalyzed by various DNA polymerases. The 4'-triphosphates of (+/-)-cis-4-hydroxymethyl-2-(1-thyminylmethyl)-1,3-dioxolane and the corresponding (+/-)-trans-isomer were shown to be terminating substrates of terminal deoxynucleotidyl transferase. 4'-Triphosphate of (+/-)-cis-4-hydroxymethyl-2-(1-thyminylmethyl)- 1,3-dioxolane terminates the DNA synthesis catalyzed by HIV reverse transcriptase, whereas 2'-triphosphate of (+/-)-cis-2-hydromethyl-4-(1-thyminylmethyl)-1,3-dioxolane is a terminator in the DNA synthesis catalyzed by HIV reverse transcriptase and the Klenow fragment of DNA polymerase I.

Base Sequence↗
PubMed1992

[Achievements and prospects of the directed search for antiviral agents in the nucleoside series and their derivatives].

Recent advances of antiviral drug design among nucleosides and their derivatives have been summarized. The first chapter deals with the history of nucleic acids components and further developments in this area. Next part discusses the mechanism of action of biologically active nucleosides: 2',3'-dideoxynucleosides, acyclic analogues, phosphonate derivatives and nucleoside antibiotics. The third chapter describes planning of complicated synthesis of nucleoside analogues from branched-chain sugars and stereo-specific formation of glycosidic bond upon synthesis of ribonucleoside and 2'-deoxyribonucleoside. The last part outlines further perspectives, i. e. preparation of antiviral compounds and use of nucleoside analogues in oligonucleotide synthesis.

Antiviral Agents↗
PubMed1988

[Derivatives of C-branched monosaccharides studied by 13C NMR].

13C NMR spectra of some 3-C branched D-allofuranoses and D-ribofuranoses were obtained and interpreted. The impact of attaching the alkyl substitute to the monosaccharides on chemical shifting of the adjacent carbon atoms was shown. The experimental data are useful for elucidating structures of analogous compounds by 13C NMR.

Aminoglycosides↗
PubMed1988

[Substrate specificity of adenosine deaminase. The role of methyl groups at 2', 3', and 5'-carbon atoms of adenosine].

The substrate specifity of adenosine deaminase has been studied using C'-methyl derivatives of adenosine. On the basis of the correlation revealed between conformations of 2'- and 3'-C-methyladenosine and their substrate properties, a modified stereochemical model is suggested: the enzyme accepts the substrate within a N-type conformational range (4E----4T3----3E) of the furanose ring. The model was analysed in details using a number of C3'-modified adenosines and 5'-C-methyladenosine analogues with D-allo- and L-talo-configuration.

Adenosine↗
PubMed1984

[Study of energy characteristics of 5-fluorouracil analogs by photoionization mass-spectrometry].

The fragmentation pathways of N-1-alkoxyalkyl derivatives of 5-fluorouracil and various analogues of an antitumor drug ftorafur have been examined using a mass-spectrometry technique. The ionization and appearance energies for major ions of the compounds under study have been determined on the basis of the ionization efficiency curves obtained using photoionization mass-spectrometry. Different transport forms of 5-fluorouracil have been demonstrated to be similar in the stability of their pseudoglycosidic C-N bond.

Chemical Phenomena↗
PubMed1983

[Topochemical aspects of pyrimidine specificity of ribonuclease A].

To get insight into the origin of pyrimidine specificity of ribonuclease A, a study of the enzyme interaction with the substrate analogs having a modified nucleobase was undertaken. Pyridine and pyrimidine cyclophosphates were obtained by phosphorylation of 2'(3')-O-dibutyl stannylidene derivatives of nonprotected nucleosides in high yields. The results of kinetic and NMR studies suggested that a substrate should be locked in anti-conformation in the productive enzyme-substrate complex as it was shown for the crystalline complexes of the enzyme with pyrimidine nucleotides by X-ray analysis. The interaction between carbonyl group in position 2 of substrate nucleobase and proton accepting group of the protein (NH of Thr45) was found to be a prerequisite for the specific recognition of a substrate by the enzyme. The rate constants for transformation of lactam form (slow) and lactim form (fast) of pyrimidine substrates were estimated.

Allosteric Regulation↗
PubMed1978

[Substrate specificity of soluble mitochondrial ATPase].

The parameters of the hydrolysis of ATP and several analogs by soluble mitochondrial ATPase were determined. Vmax of the reaction decreases within the range: 2'-desoxy-ATP greater than ATP greater than etheno-ATP greater than GTP greater than 3'-O-methylATP greater than UTP. ATP, 2'-desoxypATP, 3'O-methyl-ATP, GTP, and etheno-ATP are hydrolysed by soluble mitochondrial ATPase with close Km(app) values. CTP is not hydrolysed by the enzyme and does not inhibit the ATPase reaction at a concentration of 10(-2) M. Nucleoside triphosphate derivatives with an "open" ribose cycle 9-[1',5'-dihydroxy-4-(S)-hydroxymethyl-3'-oxapent-2' (R)-yl]adenyl-5'-triphosphate, and 1-[1',5'-dihydroxy-4'-(S)-hydroxymethyl-3'-oxapent-2'(R)-yl[cytosine-5'-triphosphate are effective inhibitors of ATPase (Ki approximately 5.10(-5)M). Mitochondrial ATPase binds the ATP analogs that have hydrocarbon radicals-(CH2)2-, -(CH2)3-, and (CH2)4- instead of the ribose residues: 9-(2'hydroxyethyl)adenyl-2'-triphosphate, 9-(3'-hydroxypropyl)-adenine-3'-triphosphate, and 9-(4'-hydroxybutyl)adenine-4'-triphosphyl)adenine-4'-triphosphate were not hydrolysed by the enzyme, although they inbibit the ATPase reaction (Ki 2.10(-4)M). 9-(2'-hydroxyethyl)adenine-2'-triphosphate is hydrolysed by ATPase eight times more slowly than ATP. It is suggested that the hydrolysis of the substrates of mitochondrial ATPase is- preceded by the binding of the substrates in a tense conformation in the active site of the enzyme.

Adenosine Triphosphatases↗
PubMedDate not supplied

[Interaction of HIV-1 reverse transcriptase and bacteriophage T7 RNA polymerase with NTP phosphonate analogs and inorganic pyrophosphate].

We have examined the interaction of human immunodeficiency virus reverse transcriptase (HIV RT) and T7 RNA polymerase (T7 RNAP) with modified nucleoside triphosphates and inorganic pyrophosphate (PPi) analogs containing nonhydrolyzable bisphosphonate groups. We have synthesized a number of derivatives of bisphosphonic acid having different aromatic and nonaromatic side substituents, as well as the NTP derivatives whose incorporation into the growing nucleotide chain during the polymerization reaction results in formation of bisphosphonates as leaving groups. The competitive character of inhibition of both enzymes has been revealed for all the compounds under study, and the inhibition constants have been estimated. One of PPi analogs containing a bulky aromatic substituent is characterized by similar inhibition constants for both T7 RNAP and RT. The universal character of this inhibitor can serve as evidence for a similar structure of the NPT-binding sites in the two polymerases. It has been shown that nonsubstituted methylenebisphosphate is a better leaving group than that containing additional methyl and hydroxyl groups. The NTP analogs are very weak inhibitors of T7 RNAP, whereas HIV-1 RT is more sensitive to this type of compounds. On the basis of the X-ray crystallographic data on the T7 RNAP complex with a template and NTP, we have modeled the binding of some derivatives of bisphosphonic acid in the active center of the enzyme. The peculiarities observed in the model correlate well with the experimental data on inhibition.

DNA-Directed RNA Polymerases↗
PubMedDate not supplied

[A new approach to the synthesis of enzyme inhibitors].

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.

Binding Sites↗