Evidence for sequence-specific conformational changes in DNA from the melting temperatures of DNA phosphorothioate derivatives

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Abstract
Analogs of alternating purine-pyrimidine DNA polymers such as poly(dA-dT)-poly(dA-dT) can be made with phosphorothioate groups in the DNA backbone. A phosphorothioate diester at the 5′-purine-pyrimidine-3′ step causes a significant lowering of the polymer's melting temperature compared to a phosphorothioate diester at the 5′-pyrimidine-purine-3′ step. This may occur because sulfur substitution increases anionic charge density in the DNA minor groove and 5′-purine-pyrimidine-3′ steps narrow the minor groove. The ability to modulate charge density in the DNA backbone via sulfur substitution should prove useful in studies of sequence-dependent conformational changes in DNA.