Control of folding and binding of oligonucleotides by use of a nonnucleotide linker

A linker containing a terephthalamide group, -P(O)(O super(-))O(CH sub(2)) sub(6)NHC(O)C sub(6)H sub(4)C-(O)NH(CH sub(2)) sub(6)OP(O)(O super(-))-, is shown to be an effective structural element for organizing oligonucleotide chains in solution. Capping a pair of complementary oligonucleotides with this linker leads to marked enhancement in stability of the Watson-Crick duplex structure. Joining a pair of thymidylate oligomers with this linker gives a compound exhibiting unusually high affinity for oligo(dA) strands; even a tetramer unit can be recognized in dilute solution. Presumably Hoogsteen as well as Watson-Crick hydrogen bonding stabilizes a bimolecular "triplex". Both types of linkage (i.e., joining two complementary strands and joining two pyrimidine strands) are embodied in the novel compound, d(TTTTTT-X-TTTTTT-X-AAAAAA), and function jointly in stabilizing a doubly folded monomolecular triple stranded structure (T sub(m) 58 degree C, 1 M NaCl; -X- represents the terephthalamide linker group).