REACTIVE DERIVATIVES OF PHOSPHOROTHIOATE OLIGONUCLEOTIDE ANALOGS .1. SELECTIVE ACTIVATION OF TERMINAL PHOSPHATES AND PREPARATION OF PHOSPHAMIDE DERIVATIVES OF PHOSPHOROTHIOATE OLIGONUCLEOTIDE ANALOGS
Nv. Amirkhanov et Vf. Zarytova, REACTIVE DERIVATIVES OF PHOSPHOROTHIOATE OLIGONUCLEOTIDE ANALOGS .1. SELECTIVE ACTIVATION OF TERMINAL PHOSPHATES AND PREPARATION OF PHOSPHAMIDE DERIVATIVES OF PHOSPHOROTHIOATE OLIGONUCLEOTIDE ANALOGS, Bioorganiceskaa himia, 21(5), 1995, pp. 365-375
Selective activation of the terminal phosphates of oligonucleotide ana
logs containing internucleotide phosphorothioate groups was carried ou
t using the triphenylphosphine-dipyridyldisulfide reducing-oxidizing p
air. This formed the basis for a new method of synthesizing various de
rivatives of phosphorothioate oligonucleotide analogs. Using this meth
od, zwitterionic 3'-phosphamide derivatives of di- and trinucleotide p
hosphorothioates TpsTp and TpsTpsTp containing the 4-dimethylaminopyri
dine or N-methylimidazole residues were synthesized. The derivatives r
eacted almost quantitatively with amines to form, within 5 - 10 min, t
he corresponding 3'-phosphamides without cleavage of the internucleoti
de phosphorothioate groups. Alkyl ati ng derivatives of phosphorothioa
tes TpsTp(N(CH3)CH(2)RCl) and TpsTpsTp(N(CH3)CH(2)RCl) (RCl = -C6H4N(C
H3)CH2CH2Cl) were also synthesized by the proposed method. The internu
cleotide phosphorothioate residues of the oligonucleotide analogs were
stable during the synthesis in DMF. The activity of the alkylating RC
l groups in the synthesized compounds was maintained at 85 - 90%.