Synthesis by post-synthetic substitution of oligomers containing guanine modified at the 6-position with S-, N-, O-derivatives

Article abstract of DOI:10.1016/S0040-4020(01)88731-7

6-(2,4-dinitrophenyl)thioguanine phosphoramidite monomers with the 2-amino group of the base protected by either the isobutyryl or phenylacetyl group were incorporated into oligodeoxynucleotides with an automatic DNA synthesizer. N²-protection with the isobutyryl group was unsatisfactory because of the difficulty of removing it after synthesis of the oligemer. However, post-synthetic conversion of the N²-phenylacetyl protected 6-(2,4-dinitrophenyl)thioguanine gives oligomers containing 6-thioguanine, 2,6-diaminopurine, 2-amino-6-methylaminopurine, O⁶-methylguanine or guanine in high yield and purity. Potentially oligemers containing other labile functional groups at the 6-position could be produced by the procedure. DNA duplexes containing 6-thioguanine paired to cytosine had a markedly lower melting temperature (Tm) than counterparts containing G:C. However a DNA duplex containing 4-thiothymine paired to A had a Tm similar to that of a DNA duplex containing T:A. The distortion in DNA structure caused by 6-thioguanine may play a role in the biological effect of this compound.