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[Formula: see text]New phosphonate homodimers of 3'-azido-3'-deoxythymidine (AZT) and a phosphonate heterodimer of β-L-2',3'-dideoxy-3'-thiacytidine (3TC) and AZT were synthesized. The compounds demonstrated moderate anti-HIV activity. Stability of the compounds in human blood serum was studied. A correlation between anti-HIV activity and stability was defined.

A new group of terminal deoxynucleotidyltransferase (TDT) substrates, namely, non-nucleoside triphosphates (NNTP) bearing 5-substituted 2,4-dinitrophenyl fragments instead of nucleoside residues was synthesized.

Novel triphosphate derivatives bearing bulky or small groups at alpha-position attached to the triphosphate residue through linkers of different structures and lengths were synthesized and studied as substrates toward terminal deoxynucleotidyltransferase. The substrate efficacy depends on the structure of substituents, linker length, and nature of metal activator. The replacement of hydrophobic groups by small substituents decreased the substrate efficacy by about 20 times in respect to hydrophobic residues. The dependence on metal activator is the following: Co(2+)Mn(2+)Mg(2+). The model of interaction of alkyl triphosphates with linkers of different lengths bearing TdT active site is presented.

5′-O-Benzoyl-3′-(tetrazole-2”-yl)-3′-deoxythymidine and its 5”-substituted derivatives were obtained by the reaction of 5′-O-benzoyl-2,3′-anhydrothymidine with triethylammonium salts of either tetrazole or 5-substituted tetrazoles. Debenzoylation of these compounds yielded 3′-(tetrazole-2”-yl)-3′-deoxythymidine and its 5”-derivatives. Structures of two of them were confirmed by X-ray analysis. Both 3′-(tetrazole-2”-yl)-3′-deoxythymidine and 3′-(5”-methyltetrazole-2”-yl)-3′-deoxythymidine have anti-conformation with respect to the glycosidic bond, and 2′-endo-3′-exo-conformation of the sugar residue with gauche + orientation relative to the C4′-C5′ bond. 3′-(Tetrazole-2”-yl)-3′-deoxythymidine 5′-triphosphate exhibited poor termination substrate properties towards avian myeloblastosis virus reverse transcriptase and did not serve as a substrate for other employed DNA polymerases.

Two approaches for the synthesis of 3′-N-alkylated 3′-amino-3′-deoxythymidines were developed, including both the reaction of 3′-amino-3′-deoxythymidine with aldehydes followed by the sodium borohydride reduction and preparation of the triphenylphosphinimine derivative and subsequent reaction with alkyl iodide. 5′-Triphosphates of the synthesized compounds were shown to be terminating substrates for human immunodeficiency virus and avian myeloblastosis virus reverse transcriptases as well as for DNA polymerase β from rat liver. At the same time these compounds did not demonstrate the properties of a terminating substrate in DNA synthesis catalyzed by human DNA polymerases α, ∊, and I from E. coli.

5′-Phosphonates of natural 2′-deoxynucleosides and ribonucleosides were synthesized by condensation of 3′-O-acylated 2′-deoxynucleosides or 2′,3′-substituted (2′,3′-O-isopropylidene, 2′,3′-O-methoxymethylene or 2′,3′-O-ethoxymethylene) ribonucleosides. As condensing agents, either N,N′-dicyclohexylcarbodiimide or 2,4,6-triisopropylbenzenesulphonyl chloride were used. Nucleoside 5′-ethoxycarbonylphosphonates were converted into corresponding nucleoside 5′-aminocarbonylphosphonates by action of ammonia in methanol or aqueous ammonia. 5′-Hydrogenphosphonothioates of thymidine and 3′-deoxythymidine were obtained by reaction of phosphinic acid in the presence of pivaloyl chloride with 3′-O-acetylthymidine or 3′-deoxythymidine, respectively, followed by addition of powedered sulfur. 5′-O-methylenephosphonates of thymidine and 2′-deoxyadenosine were prepared by intramolecular reaction of corresponding 3′-O-iodomethylphosphonates under basic conditions. All compounds were tested for inhibition of several...

This paper deals with drug abuse among minority youth in an economically depressed community. The authors stress that the traditional anti-drug rhetoric does not prevent drug use in oppressed areas. The paper concludes that communities must provide positive and productive alternatives to drug use. Such a strategy must emphasize the development of human potential, as opposed to traditional alcohol and drug prevention programs.

A series of acyclic nucleosides and related α-phosphonyl acyclic analogues of dNTP with an amide bond have been prepared. Their antiviral and substrate properties were investigated.

The presence of reporter or ligand groups in 2′-deoxynucleoside 5′-triphosphates (dNTP) makes it possible to monitor the diffusion of these compounds into cell and to observe their incorporation into DNA. Here we present the synthesis of new dNTPs modified at α-, β,γ- or γ-phosphates of types I-IV, and containing reporter or ligand groups at the C5 position of dUTP.

Western knowledge transfer activities have come under increasing criticism in recent years for bringing about disintegration of indigenious cultures and lopsided transformations of social environments in many parts of the developing world. Responding to the need for interculturally responsible technology transfer practices, this paper reviews some of the principal concerns, and advances a methodological justification for change management based upon the joint coordination of pertinent cultural relevance structures. By treating cultures and their technological artifacts as elaborate sign system designs, it introduces a method of indexing social and cultural interaction with novel (transferred) technologies. This index is called the “Social‐Cultural Receptivity Index”; or SCRI.