2'-O-alkyl polynucleotides. I. Novel procedure for the synthesis of 2'-O-alkyl nucleotides

Polynucleotides containing hybrid sequences. Synthesis of oligonucleotides possessing a single ribonucleotidyl-(3',5')-deoxyribonucleotide linkage

“…2'chloro-2'-deoxyuridine and 2'-chloro-2'-deoxycytidinc (Hobbs et al, 1972b), 2'-0ethyladenosine (Khurshid et al. 1972;Tazawa et al, 1972), and 2'-amino-2'-deoxyuridine (Hobbs et al, 1972a) are all capable of polymerizing to high molecular weight molecules in the presence of the enzyme. All of these substrates as well as the common ribonucleoside diphosphates possess electronegative atoms attached to their €5positions and it is possible that this may be one of the structural requirements for enzymatic polymerization.…”

2'-0-(α-Methoxyethyl)nucleoside 5'-diphosphates as single-addition substrates in the synthesis of specific oligoribonucleotides with polynucleotide phosphorylase

“…The simplest explanation to account for the differences in activity (polymerization vs. single addition) of the various 2'-substituted diphosphates would involve a consideration of the steric hindrance of the reactivity of the 3' hydroxyl group of the oligonucleotide by the substituent group at the 2' position after the first addition to the primer molecule has been made. It has recently been shown that 2'-0-ethyladenosine 5'diphosphate can be polymerized by polynucleotide phosphorylase (Tazawa et al, 1972) so that the -methoxyethyl group may well be the smallest substituent that is capable of restricting the reaction to single addition. In this regard it would be of some interest to synthesize and test the activity of a 2'-O-isopropylnucleoside 5'-diphosphate.…”

“…by the use of manganous ion as cofactor (Babinet et al, 1965;Thang et al, 1965;Zmudzka et al, 1969a,b;Rottman and Heinlein, 1968; Chou and Singer, 1971;Torrence and Witkop, 1972;Mackey and Gilham, 1971) or possibly through the use of matrix-bound enzyme (Brentnall and Hutchinson, 1972). By such techniques, a number of polynucleotides containing 2'-fluoro (Janik et al, 1972;Hendler et al, 1971), 2'-amino (Hobbs et al, 1972a), 2'-chloro (Hobbs et al, 1971(Hobbs et al, , 1972b, 2'-0-methyl (Zmudzka et al, 1969a,b;Rottman and Heinlein, 1968;Zmudzka and Shugar, 1970;Tazawa et ah, 1972), and 2'-O-ethyl (Khurshid et al, 1972;Tazawa et al, 1972) substituents have been introduced and studied recently. Such 2'-modified polynucleotides can be powerful tools in the elucidation of the role of the 2 '-hydroxyl group in RNA and the factors responsible for the clinically promising phenomenon of the induction of interferon by synthetic polynucleotides (Colby, 1971; KJeinschmidt, 1972).…”

Influence of 2'-O-alkylation on the structure of single-stranded polynucleotides and the stability of 2'-O-alkylated polynucleotide complexes

“…Although we have earlier reported a study utilizing poly(Im) (Gerard et al, 1972), its synthesis and characterization were not described. Recently Tazawa et al (1972) have also reported the synthesis of poly-(Im). Since this polynucleotide presents some unique problems in isolation its preparation will be briefly outlined.…”