Nucleic Acids Research, 1986, Vol. 14, No. 8 3487-3499
© 1986
Articles |
Effects of pendant groups at phosphorus on binding properties of d-ApA analogues
Department of Chemistry and Department of Biochemistry, Molecular Biology and Cell Biology Northwestern University, Evanston, IL 60201, USA
*To whom correspondence should be addressed
Received February 12, 1986. Revised March 25, 1986. Accepted March 25, 1986.
The Interaction of several synthetic analogues of d-ApA with Poly U and Poly dT was examined to explore the effects of substituents at phosphorus on binding properties of oligonucleotides. These analogues contained a bulky, lipophilic group (2,2,2-trichloroethoxy or 2,2,2-trichloro-1,1-dlmethylethoxy) a small, uncharged hydrogen-bonding group (amido), or a cationic phosphoramidate (2-aminoethylamido, protonated in neutral aqueous media) in place of the anionic oxygen of the internucleotide phosphate. As determined by "melting curves" each formed a complex with Poly U more stable than the Poly U d-ApA complex. Binding to Poly dT was comparable or in some cases stronger. Checks on composition (mixing curves) revealed the expected stoichiometry of 1dA:2U (or 2dT). Stereochemistry at phosphorus influenced stability of the complexes, but the effect was not a major one. These results suggest that oligonucleotides containing large, lipophilic groups, as well as small non-ionic groups (e.g., the methyl phosphonates) or polar groups, could be useful as probes in hybridization experiments.