BIOCHEMICAL PROPERTIES OF 5‐SULFUR‐SUBSTITUTED PYRIMIDINE NUCLEOSIDES AND NUCLEOTIDES^*

Structure-activity relationships and mode of action of 5-mercapto-substituted oligo- and polynucleotides as antitemplates inhibiting replication of human immunodeficiency virus type 1

“…These partially thiolated polynucleotides were found to inhibit various RNA and DNA polymerases by effectively competing with the functional templates or primers for their binding sites on the enzymes and thus blocking their functions (6,29). In particular, the reverse transcriptases (RTs) of RNA tumor viruses (11,12,30), the herpes simplex virus-induced DNA polymerase (10), and the DNA polymerase a of mammalian cells (29,32) were found to be sensitive to inhibition by 5-thiolated polynucleotide antitemplates.…”

Structural characterization of partially thiolated poly(cytidylic acid)

“…(B) Determination of the Percent of Thiolated Bases in the Modified Polynucleotides. The ultraviolet spectrum of the partially thiolated polycytidylate at neutral pH showed a similar absorption maximum to that of the unmodified poly-(cytidylic acid); however, upon the addition of DTT, a second absorption maximum appeared in the 330-335-nm region, indicating the presence of the ionized 5-mercapto groups (Bardos et al, 1975). Thus, it appears that in the process of conversion to the sodium salt and purification of MPC in aqueous solution most of the SH groups were oxidized to disulfides and the addition of DTT is required to reduce them to the free thiols.…”

“…At pH 7.5, poly(C) exists as a single-stranded helix stabilized by the hydrophobic interaction between the stacked bases (Fasman et al, 1964;Arnott et al, 1976). In the case of MPC, in the presence of DTT at pH 7.5, the mercapto groups are completely ionized (Bardos et al, 1975). This anionic character of the 5-mercaptocytidylate residues may disturb the continuity of base stacking of the polynucleotide chain presumably due to the polarity of the thiolate ions randomly distributed throughout the polymer and to the clustering of water molecules around them which would derange the hydrophobic forces.…”

“…At pH 4.0, the double-stranded helix of poly(C) is stabilized by the hydrogen bonds involving the carbonyl and amino groups of each pair of cytosine residues as well as by the sharing of an additional proton between the N3 nitrogens of the two bases (Akinrimisi et al, 1963;Langridge & Rich, 1962). In the case of MPC, zwitterion formation would occur at pH 4.3 between the 4-amino and 5-thiol groups of the 5-mercaptocytosine moieties (Bardos et al, 1975). This would prevent protonation at N3 and thus weaken the hydrogen bonding with the "complementary" cytosine of the other strand.…”

Synthesis of some new S-alkylated derivatives of 5-mercapto-2'-deoxyuridine as potential antiviral agents

“…against HSV-1, its S-methyl derivative(2) demonstrated significant anti-herpes activity 20,21. This was in contrast to the reported inactivity of the analogous 5-methoxy-2'deoxyuridine.21 Subsequent studies using 14C-labeled 5-(S-methylmercapto)-2'-deoxyuridine indicated that the mode of action of 2 as an antiviral agent is apparently…”