Triplex Formation by Oligonucleotides Containing Organomercurated Base Moieties.

Abstract

Homothymine oligonucleotides with a single 5-mercuricytosine or 5-mercuriuracil residue at their termini have been synthesized and their capacity to form triplexes has been examined with an extensive array of double-helical targets. UV and circular dichroism (CD) melting experiments revealed the formation and thermal denaturation of pyrimidine⋅purine*pyrimidine-type triple helices with all oligonucleotide combinations studied. Nearly all triplexes were destabilized upon mercuration of the 3'-terminal residue of the triplex-forming oligonucleotide, in all likelihood due to competing intramolecular HgII -mediated base pairing. Two exceptions from this general pattern were, however, observed: 5-mercuricytosine was stabilizing when placed opposite to a T⋅A or A⋅T base pair. The stabilization was further amplified in the presence of 2-mercaptoethanol (but not hexanethiol, thiophenol or cysteine), suggesting a stabilizing interaction other than HgII -mediated base pairing.