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Steroid−DNA Interactions Increasing Stability, Sequence-Selectivity, DNA/RNA Discrimination, and Hypochromicity of Oligonucleotide Duplexes

1999; American Chemical Society; Volume: 121; Issue: 47 Linguagem: Inglês

10.1021/ja9920415

1943-2984

Colleen F. Bleczinski, Clemens Richert,

RNA Interference and Gene Delivery

Cholic acid and its deoxy derivatives were found to increase the melting point of oligonucleotide duplexes when coupled to their 5'-termini. For duplexes of mixed-sequence octamers, the melting point was 8−11 °C higher with the steroid appendage than without. For the self-complementary hexamer TGCGCA, a 21 °C melting point increase was measured in the presence of steroid appendage and −18 kcal/mol in ΔΔH°. The affinity increases were accompanied by increased discrimination against mismatches at the two terminal base pairs and increased hypochromicity, as well as an improved DNA/RNA discrimination for the non selcomplementary sequence. Cross-peaks in the NOESY spectrum of (chl-T*GCGCA)2, where chl denotes the cholic acid residue and T* a 5'-amino-5'-deoxythymidine residue, point toward stacking interactions in which the methyl groups of the steroid face the nucleobases. Our results indicate that bile acids can form a specific complex with terminal T:A base pairs of double-stranded DNA.