Porphyrin substituted phosphoramidites: new building blocks for porphyrin–oligonucleotide syntheses

Abstract

Thymidine phosphoramidites containing trispyridylphenyl and tetraphenylporphyrin chromophores attached via a short amide linker in the 3′-position have been synthesized and used as building blocks in solid-phase synthesis of self-complementary 8-mer oligonucleotides 3′-T-5′-GCGCGCA-3′ and 5′-ACGCGCGT-3′. To our knowledge, these are the first porphyrin–oligonucleotide conjugates carrying the porphyrin chromophores in the 3′-position. Chain assembly was achieved by automated solid-phase synthesis and by inexpensive straightforward ‘in flask’ modification of commercially available solid supported oligonucleotides. This approach allows the synthesis of modified oligonucleotides without using costly instrumentation for automated DNA synthesis. Porphyrin-containing self-complementary oligonucleotides are expected to be a valuable model for drug binding studies and determination of conformational changes in DNA sequences using circular dichroism.