[S,X-acetals in nucleoside chemistry. II. Synthesis 3'-O-methylthiomethyl derivatives of ribonucleosides]. / S,X-atsetali v khimii nukleozidov. II. Sintez 3'-O-metiltiometil'nykh proizvodnykh ribonukleozidov.

3'-O-Methylthiomethyl derivatives of ribonucleosides were synthesized from the selectively protected nucleosides by the action of a dimethyl sulfide-benzoyl peroxide mixture in acetonitrile or a dimethyl sulfoxide-acetic anhydride-acetic acid mixture.

[The S,X-acetals in nucleoside chemistry. I. The synthesis of 2'- and 5'-O-methylthiomethyl ribonucleosides]. / S,X-atsetali v khimii nukleozidov. I. Sintez 2'-i 5'-O-metultiometil'n ykh proizvodnykh ribonukleozidov.

Ribonucleoside 2'- and 5'-methylthiomethyl derivatives were synthesized from selectively protected nucleosides by the action of dimethyl sulfoxide-acetic anhydride-acetic acid mixture.

[X-ray structural study of 3'-O-methylthiomethylthymidine and 3'-O-methylsulfinylmethylthymidine--potential inhibitors of HIV]. / Rentgenostrukturnoe issledovanie 3'-O-metiltiometiltimidina i 3'-O-metilsul'finilmetiltimidina--potentsial'nykh ingibitorov VICh.

The molecular and crystalline structures of deoxiribonucleoside analogs: 3'-O-methylthiomethylthymidine monohydrate dT(CH2SMe).H2O and 3'-O-methylsulphinylmethylthymidine dT(CH2SOMe) were determined. The space group of dT(CH2SMe).H2O crystals is P2(1), the parameters of the elementary cell are a = 10.417(1), b = 4.912(2), c = 15.969(2) A, beta = 107.23(1) degrees, V = 780.5 A3, Z = 2, R = 3.8%. The crystals of dT(CH2SOMe have a space group P2(1)2(1)2(1), the elementary cell parameters are a = 8.858(2), b = 9.303(1), c = 17.698(2) A, V = 1458.3 A3, Z = 4, R = 2.8%. The dT(CH2SMe) and dT(CH2SOMe) molecules are characterized by an anti-conformation relative to the glycoside bond (angles chi (O4'-C1'-N1-C2) are equal to -116.2 degrees and -148.8 degrees), a gauche(+)-conformation relative to the exocyclic bond C4'-C5' (angles phi CO (C3'-C4'-C5'-O5') are equal to 52.1 degrees and 41.1 degrees). The conformation of the furanose cycle in the dT(CH2SMe) molecule is described by C2'-endo-C3'-exo (P = 167.8 degrees, psi m = 34.8 degrees) and in the dT(CH2SOMe) molecule by C2'-endo-C1'-exo (P = 148.4 degrees, psi m = 35.4 degrees). The structures studied were compared with 3'-azido-3'-deoxythymidine (AZT) and thymidine.

[The effect of kemantane on T-helpers and T-suppressors]. / Vliianie kemantana na T-khelpery i T-supressory.

The study of Kemantan on functionally alternative humoral immunity regulator cells: T-helpers and antigen-specific T-suppressors, including their induction, accumulation and functioning, was studied. Kemantan in doses of 0.2-200 mg/kg, introduced to the donors of T-helpers 2 days before they were taken, stimulated their activity 1.5- to 2-fold (with p less than 0.05). Kemantan had no influence on the functional activity of T-suppressors, as well as on their induction and accumulation.

[The structure and antiviral activity of ribavirin analogs. I. Molecular and crystal structure of 1-(2-hydroxyethoxymethyl)-1,2,4-triazole-5-carboxamide]. / Struktura i protivovirusnaia aktivnost' analogov ribavirina. I. Molekuliarnaia i kristallicheskaia struktura 1-(2-gidroksiétoksimetil)-1,2,4-triazol-5-karboksamida.

The crystal and molecular structures of the antiviral compound 1-(2-hydroxyethoxymethyl)-1,2,4-triazole-5-carboxamide has been determined by the X-ray diffraction method. The space group is P2i/c, unit cell parameters a = 4,381, b = 18,679, c = 10,776 A, beta = 107,40 degrees, Z = 4. The structure was solved by the direct method and refined by a full-matrix least-squares procedure to R = 4.9%. Two planar groups of atoms can be distinguished in the molecule. The first group involves the atoms of triazole ring, C6, and C1', the second one contains C5, C6, O6 and N6 atoms. The angle between these planes is 5.6 degrees. The carboxyamide group is rotated by 180 degrees in comparison with this group in ribavirin. That is why the intramolecular hydrogen bond C1'-H1'. 1...O6 can form. Torsion angle O5'-C5'-C4'-O4' is 73.9 degrees and it corresponds to gauche-rotamer. The conformation about O4'-C4' bond is trans. The C1'-C4' bond is approximately perpendicular to the aglycone.

[The structure and antiviral activity of ribavirin analogs. II. Molecular and crystal structure of 1-(1,5-dihydroxy-3-oxapent-2-yl)-1,2,4-triazole-5-carboxamide]. / Struktura i protivovirusnaia aktivnost' analogov ribavirina. II. Molekuliarnaia i kristallicheskaia struktura 1-(1,5-digidroksi-3-oksapent-2-il)-1,2,4-triazol-5-karboksamida.

X-ray structure of the title compound, an antiviral agent moderately active towards Herpes simplex virus type 1, has been determined. The space group is P2i/n, unit cell parameters: a = 10,119, b = 7,529, c = 13,585 A, beta = 107,82 degrees, Z = 4. The structure was solved by the direct method and refined by least-squares procedure to R = 2.9%. The gauche-conformation about C4'-C5' bond and trans-conformation about O4'-C4' bond are realized in the molecule. The carboxyamide group at the C5 atom of triazol cycle provides a steric opportunity for the intramolecular hydrogen bond C1'-H1'...O6 formation.

Acyclic analogs of nucleosides. Synthesis of hydroxyalkyl derivatives of 2-trifluoromethyl- and 2-trifluoromethylthiobenzimidazole.

1-(2,3-Dihydroxypropyl)-, 1-(4-hydroxy-2-oxabutyl)-, 1-(3-hydroxymethyl-4-hydroxy-2-oxabutyl)-, 1-(1,5-dihydroxy-3-oxa-2-pentyl)-, 1-(5-hydroxy-3-oxa-2-pentyl)-, and 1-(4,5-dihydroxy-2-oxapentyl)-2-trifluoromethyl- and -2-trifluoromethylthiobenzimidazoles were obtained by condensation of trimethylsilyl derivatives of 2-substituted benzimidazoles with alkylating agents in the presence of SnCl4, or by direct alkylation of the sodium salts of the heterocycles.

[Synthesis of acyclic analogs of ribavirin]. / Sintez atsiklicheskikh analogov ribavirina.

A number of ribavirin analogues were prepared in which the ribose moiety was replaced with acyclic substituents imitating some fragments of the ribose ring: 2,3-dihydroxy-prop-1-yl, 3-hydroxymethyl-4-hydroxy-2-oxabut-1-yl, 4,5-dihydroxy-2-oxapent-1-yl and 1,5-dihydroxy-3-oxapent-2-yl. These analogues were synthesized by direct alkylation of ethyl 1,2,4-triazole-3-carboxylate with suitable agents followed by ammonolysis. New convenient methods for preparing the alkylating agents were developed.

[X-ray study of an antiviral agent (S)-9-(2,3-dihydroxypropyl)adenine]. / Rentgenostrukturnoe issledovanie protivovirusnogo agenta (S)-9-(2,3-dioksipropil)adenina.

The molecular and crystal structures of the antiviral compound, (S)-9-(2,3-dihydroxypropyl)adenine, was established. The space group is P21, unit-cell parameters a 5,546(1), b 8,381(1), c 10,119(1), beta 91,979(9) degrees, Z2. The structure was solved by the direct method and refined by a full-matrix least-squares procedure to R 4,2%. All non-hydrogen atoms of this compound are concentrated in two planes. The first one involves the atoms of the purine moiety and N(6) and C(1'), while the second one accommodates C(2'), C(3'), O(2') and O(3'). The angle between these planes is 54,3 degrees. The conformation of the compound in crystal was compared with that deduced from theoretical analysis.

[Isolation and characteristics of a mutant herpes simplex virus type 1 resistant to phosphonoacetic acid]. / Vydelenie i kharakteristika mutanta virusa gerpesa prostogo tipa 1, rezistentnogo k fosfonouksusnoi kislote.

By successive passages and triple cloning of herpes simplex virus type 1 (HSV-1) in Vero cell culture in the presence of increasing concentrations of phosphonoacetic acid (PAA) a mutant of HSV-1 resistant to PAA (PAAr) was derived and characterized. The resistance to the inhibitor was transmitted from PAAr-mutant to a sensitive strain (L2) by recombination performed by the marker rescue method using DNA fragmented by Hpa-1 restrictase. The resulting recombinant (R-551) was resistant to the inhibitor and had an altered primary structure of DNA.

[Resistance of various herpes simplex virus strains to the action of chemical inhibitors]. / Izuchenie tsoichivosti razlichnykh shtammov virusov gerpesa prostogo k deistviiu khimicheskikh ingibitorov.

The effect of chemical inhibitors on reproduction of 2 laboratory and 3 vaccine strains of herpes simplex virus (HSV), types 1 and 2, was studied. By the time of the study the vaccine strains had undergone from 27 to 69 passages in chick embryo fibroblast cultures. All the vaccine strains (L2, Us, and VN) exhibited 100-1000 fold higher resistance to phosphonoacetic acid than did the laboratory F+ and G strains, and the vaccine L2 strain (HSV-1) was also 1000-fold resistant to 1-beta-D-arabinofuranosine thymine.

[Polyclonal activation of B-lymphocytes by synthetic polyelectrolytes]. / Poliklonal'naia aktivatsiia B-limfotsitov sinteticheskimi poliélektrolitami.

A study was made of the ability of polyacrylic acid, poly-4-vinylpyridine, and the copolymers 4-vinylpyridine and 4-vinyl-N-alkylpyridinium bromides with side hydrocarbonic radicals of varying length to induce in mice of different strains B-cell differentiation into the plaque-forming cells without antigenic stimulation. The polyelectrolytes have been shown to favour the transformation of B lymphocytes to the cells that secrete polyclonal antibodies, i.e. to be polyclonal activators of B lymphocytes. B lymphocyte differentiation induced by the polyelectrolytes does not depend on T cells and is liable to genetic restriction.

[Peptidyl transferase center of ribosomes. I. Difference in the substrate specificity of the acceptor and donor portions]. / Peptidiltransferaznyi tsentr ribosom. I. Razlichie v substratnoi spetsifichnosti aktseptornogo i donornogo uchastkov.

Some model substrates of the peptidyl transferase centre of E. coli MRE-600 ribosomes were synthesised and tested in a cell-free system without a template. In these substances the nucleic bases were linked covalently with the ribose residue or had a limited rotation about the glycosidic bond. 3'(2')-O-(N-formylmethionyl)-8-bromoadenosine 5'-phosphate and 3'(2')-O-phenylalanyl-8,5'-anhydro-8-mercaptoadenosine were shown to possess a high peptide donor and acceptor activity correspondingly. Contrary to that 3'(2')-O-phenylalanyl-8-bromoadenosine was practically inactive as a peptide acceptor and 3'(2')-O-(N-formylmethionyl)-8,5'-anhydro-8-mercaptoadenosine had no peptide donor activity at all. PMR and CD spectra of the compounds synthesised were investigated. The significance of conformation of the model substrates on their activity is discussed.