ABSTRACT

This chapter explains that single-stranded circular oligonucleotides can display nuclease resistance, binding affinity, and sequence selectivity which are superior to those of linear structures. Such characteristics may eventually prove to be advantageous in the sequence-specific inhibition of gene expression. The chapter discusses the design and synthesis of cyclic oligonucleotides, their hybridization, and possible strategies for their eventual biological use. It describes circular oligonucleotides which are not internally selfcomplementary. Comparison of binding affinities of circular and linear oligodeoxynucleotides for a complementary strand of DNA shows that circular structures can have a very large binding advantage. The strength of binding of a circular oligonucleotide is, as with all DNA complexes, dependent on the conditions in solution. One backbone modification which the authors have been pursuing is the replacement of the 5-nt loops with a single nonnucleotide bridging group. In addition, if a linker is more rigid than the original five nucleotides, it has the potential for increasing binding strength even further.