Modified polynucleotides. VII. Impaired integrity of a synthetic DNA containing the antiherpetic agent 5-isopropyl-2'-deoxyuridine

Abstract

5–Isopropyl–2'–deoxyuridine (ip⁵dU) was recently recognized as a clinically useful antiherpetic (HSV–l) agent. An ip⁵dU–containing polynucleotide, poly(dA–dT, ip⁵dU) was prepared to study how physical and bio–organic properties of the synthetic DNA model poly(dA–dT) would change upon partial substitution of thymidine. Synthesis was carried out with DNA polymerase enzyme and the polymers contained 7–9% of ip⁵dU. It proved to be less thermostable than poly(dA–dT) and the transition width was highly increased. Although it was a very efficient template for DNA polymerase enzyme, template activity for RNA synthesis was strongly reduced by the presence of ip⁵dU. Diminished stability against enzymic degradation, especially against single –strand–specific Nuclease S1 was also observed.