The 6-thioguanine/5-methyl-2-pyrimidinone base pair

Abstract

As part of a program to determine the physical possibility of expanding the number of types of base pairs in DNA, the pairing stabilities of the analog bases 6-thioguanine (GS) and 5-methyl-2-pyrimidinone (TH) in oligodeoxynucleotides were measured. Procedures were developed to synthesize oligodeoxynucleotides with the analog bases. The sequences of the synthesized oligomers were T-C-G-A-C-G-G-X-Y-C-C-G. An enzymatic procedure was developed to measure relative association constants of oligomer pairs with the self complementary reference oligomer, X = A and Y = T, K(T/A) = K. The results were K(C/G) = (5 +/- .5)K, K(TH/GS) = K/(1 +/- .5), K(T/G) = K/(9 +/- 3), K(TH/G) = K/(25 +/- 5), K(C/GS) less than K/30, K(TH/A) less than K/40, K(T/GS) less than K/40, K(C/A) less than K/40. The results with the standard bases are consistent with other methods of measurement. The stability of the base pair GS/TH is approximately the same as the standard base pair A/T.

Human MutSalpha recognizes damaged DNA base pairs containing O6-methylguanine, O4-methylthymine, or the cisplatin-d(GpG) adduct.

“…30 and 36), an effect that may be due to structural similarities between S6G and O6meG (30,37 The specificity of hMutSa for the cisplatin 1,2-d(GpG) adduct was further assessed by competition methods. Complexes of the human protein with a 31-bp G-T heteroduplex or a 32-bp duplex containing a cisplatin 1,2-d(GpG) crosslink were similarly resistant to competition by a 31-bp homoduplex competitor, with binding reduced only 20-40% by a 160-fold molar excess of the competing DNA (Fig.…”

Incorporation of 2'-Deoxy-6-thioguanosine into G-Rich Oligodeoxyribonucleotides Inhibits G-Tetrad Formation and Facilitates Triplex Formation

“…Although a few reports have appeared in the literature describing the synthesis of S6-dG-containing oligonucleotides (Bronstein et al, 1988;Rappaport, 1988;Richardson & Bronstein, 1989), none of these syntheses considered protecting the thione group of S6-dG, which is of paramount importance in order to mask its nucleophilicity and prevent oxidative hydrolysis. The formation of the dimeric disulfides can also be expected in sulfur-containing nucleotides.…”

Self-destruction and tolerance in resistance of mammalian cells to alkylation damage

“…The only other modified DNA base that is known to be subject to this type of tolerance is 6-thioguanine (6-TG) which exerts its effect via its incorporation into DNA. 06-meGua and 6-TG have closely similar molecular volumes and they also share the property of being unable to form a stable base pair with either of the normal pyrimidines (70). The cross-resistance of tolerant cells to 6-TG and 06-meGua, together with their unaltered sensitivity to DNA ethylation indicates that an important feature of the tolerated base is its similarity to normal guanine.…”