Nucleic Acids Research, 1988, Vol. 16, No. 8 3209-3221
© 1988
Articles |
Physicochemical properties of phospborothioate oligodeoxynucleotides
Clinical Pharmacology Branch, National Cancer Institute NIH, Bethesda, MD 20892, USA
Received January 25, 1988. Revised March 16, 1988. Accepted March 16, 1988.
We have recently shown that phosphorothioate (PS) oligodeoxynucleotide (ODN) analogs, unlike their normal congeners, exhibit significant anti-HTV activity (Matsukura et al., (1987) Proc.Natl.Acad.Sci.USA 84, 7706–7710). We now report the syntheses, melting temperatures (Tm), and nuclease susceptibilities of a series of phosphorothioate ODN analogs. These include all-PS duplexes, duplexes with one normal chain and the other chain either all-PS, or end-capped with several PS groups at both 3' and 5' ends. The DNase susceptibilities of the S-ODNs are much less than the normal phosphodiesters, but by contrast duplexes of poly-rA with S-dT40 are much more susceptible to RNase H digestion. The Tm's for AT base pairs of S-ODNs are significantly depressed relative to normals, while GC base pairs show much less Tm depression. The Tm's of S-dT oligomers with poly-rA are reduced relative to the duplexes with normal dA oligomers. These results have significance for the biological properties of these analogs as anti-message inhibitors of gene expression, and provide a rational basis for the S-dC/G sequences as potential effective anti-AIDS agents.
*Current address: Mitsubishi Institute of Life Sciences, Tokyo, Japan.
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