Abstract
The hybridization of exogenous oligonucleotides to cellular RNA and DNA offers a means to modulate the expression of specific genes, with applications in the treatment of viral infections, cancer and other diseases. The covalent attachment (conjugation) of various low molecular weight compounds to these molecules has proved particularly useful in improving their pharmacodynamics, pharmacokinetic and hybridisation properties. The conjugation of small molecules that interact with nucleic acids through intercalation, edge and groove binding has been shown to improve the strength and specificity of oligonucleotide hybridisation, whilst the conjugation of compounds that chemically react with nucleic acids has been used to invoke cross-linking and cleavage reactions at oligonucleotide target sites. The aim of this review is to summarize the properties of some of these small molecule-oligonucleotide conjugates, with an emphasis on their biological applications.
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