SYNTHESIS BY POST-SYNTHETIC SUBSTITUTION OF OLIGOMERS CONTAINING GUANINE MODIFIED AT THE 6-POSITION WITH S-DERIVATIVES, N-DERIVATIVES, O-DERIVATIVES

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 oligomer. 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 oligomers 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 their 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.