Effect of thiobase incorporation into duplex DNA during the polymerization reaction.
6-Thioguanine, a thioderivative of the nucleic acid base guanine, is a metabolic inhibitor and possesses antitumor activity. In addition, it inhibits the synthesis of nucleotides and is incorporated readily into the nucleic acid during the polymerization reaction by substituting for guanine. The biological activity of 6-thioguanine has been related to the alterations in the dimensions and energetics of a duplex DNA as a result its incorporation in place of guanine (Bugg and Thewalt 1975). With the advancement in the computer hardware technology and emergence of sophisticated molecular modeling packages, it is now possible to simulate the biological activities of different drugs. An effort has been made to explain the biological activities of thoiderivatives of nucleic acid bases. For this, semiempirical MNDO quantum chemical calculations were performed on some non-complementary (thiosubstituted) base pairs to understand the effects of substitution of sulfur for oxygen in nucleic acid bases. The base pairs considered in this study are thioguanine-cytosine (TG-C), guanine-thiocytosine (G-TC) and thioguanine-thiocytosine (TG-TC). The results obtained suggest that the replacement of guanine by thioguanine and/or replacement of cytosine by thiocytosine weakens the stability of the double helical DNA by reducing the strength of the hydrogen bonds.
Singh
K
K
Department of Ophthalmology, UMD-New Jersey Medical School, Newark 07103, USA.
Groth-Vasselli
B
B
Farnsworth
P N
PN
Rai
D K
DK
D001704:Biopolymers; D004247:DNA / Q000737:chemistry*; D006860:Hydrogen Bonding; D013816:Thermodynamics
D001704:Biopolymers; D004247:DNA