[structure: see text] To study the structural requirements of aminoglycoside binding to nucleic acids, compound 1-an analogue of the naturally occurring nucleoside J-was synthesized. When incorporated into oligodeoxynucleotides, 1 leads to thermal stabilization of the resulting duplexes. The increase in pairing affinity is stronger with complementary RNA than with DNA.

The preparation of diene-modified oligonucleotides as well as their properties and further derivatization are described. Self-complementary oligonucleotides containing a diene moiety in the loop region form stable, hairpin-like secondary structures. These hairpin mimics can be further derivatized via the Diels-Alder reaction. Diene modification in the stem region leads, in contrast, to a marked destabilization of the hairpin structure. No further reduction in stability is observed, however, upon conjugation of the stem-modified derivatives via the Diels-Alder reaction with an N-substituted maleimide dienophile.

A highly stable 1,3-butadiene-derived DNA hairpin mimic and its derivatisation via the Diels-Alder reaction with various dienophiles are described.

The chemical crosslinking of modified nucleic acids via the Diels-Alder reaction is reported. For this purpose, 1,3-butadiene derived building blocks were incorporated into complementary oligodeoxynucleotides. Treatment of the obtained duplex with difunctional dienophiles results in the clean crosslinking of the two strands. Non-crosslinked adducts arising from a single Diels-Alder reaction of a maleimide to only one strand were not observed, indicating that the first reaction is the rate determining step of the overall process. Based on their thermal denaturation profiles, the crosslinked hybrids behave like two separate, hairpin-like structures, rather than like a single, continuous duplex.

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