Hammerhead cleavage of the phosphorodithioate linkage

Wesley B. Derrick, Charles H. Greef, Marvin H. Caruthers, Olke C. Uhlenbeck*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


Under standard reaction conditions, a hammerhead ribozyme with a phosphorodithioate linkage at the cleavage site cleaved to the expected products with a rate about 500-fold slower than the corresponding phosphodiester linkage. When the greater stability of the dithioate linkage to nonenzymatic nucleophilic attack is taken into account, the hammerhead is remarkably effective at cleaving the dithioate linkage considering that the R(p)-phosphoromonothioate linkage is virtually inactive. On the basis of experiments determining the Mg2+ concentration dependence of the cleavage rate and the stimulation of cleavage by thiophilic Cd2+ ion, the lesser catalytic rate enhancement of the dithioate linkage is primarily due to the loss of a single Mg2+ ion bound near the cleavage site. These results are qualitatively similar to, but quantitatively different from, similar experiments examining the hammerhead cleavage properties of the R(p)- phosphoromonothioate linkage. The dithioate linkage thus promises to be a valuable alternative phosphate analogue to the monothioate linkage in studying the mechanisms of RNA catalysis.

Original languageEnglish (US)
Pages (from-to)4947-4954
Number of pages8
Issue number16
StatePublished - Apr 25 2000

ASJC Scopus subject areas

  • Biochemistry


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