Chemistry of minor groove binder-oligonucleotide conjugates

Abstract

Various types of minor groove binders have been attached to synthetic oligodeoxynucleotides, and the interactions of these conjugates (MB-ODNs) with DNA are reviewed here. MB-ODNs have enhanced DNA affinity and have improved the hybridization properties of sequence-specific DNA probes. Short MB-ODNs hybridize with ssDNA to give more stable DNA duplexes than unmodified ODNs with similar lengths. Mismatch discrimination of short MB-ODNs is enhanced in comparison to longer unmodified ODNs. The stronger binding of MB-ODNs allows for more stringent hybridization conditions to be used in DNA probe-based assays. MB-ODNs are especially useful in quantitative "real-time" PCR assays since they bind efficiently during the high-temperature primer extension cycle. The synthesis and biophysical chemistry of MB-ODN conjugates are reviewed here. Four published structural classes of MB-ODNs and their various dsDNA binding modes are discussed, and the well-characterized DPI3-type MB-ODNs and their interactions with ssDNA target strands are described in detail.