The thermal stability of oligonucleotide duplexes in dilute aqueous solution can be increased by capping the termini with covalent linkers. Stilbenedicarboxamide bridges have proved particularly effective. To test the limits of such stabilization, wehave synthesized the small cyclic oligonucleotide conjugate 2. which contains the four common nucleotides and two Stilbenedicarboxamide bridges. With the capacity to form only two base pairs. 2 represents a minimal nucleotide construct that could make a"mini DNA duplex" by base stacking. We show here that 2 indeed adopts a remarkably stable conformation in neutral solution at room temperature that "melts out" on heating and switches in alkaline solution to a novel conformation that bring the stilbene groups in juxtaposition.
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