SYNTHESIS AND CHARACTERIZATION OF POLYAMINE-BASED BIOMIMETIC CATALYSTS AS ARTIFICIAL RIBONUCLEASE

Abstract

Several polyamine derivatives (I–V) conjugated with or without an intercalative moiety were prepared as ribonuclease mimics. Although no DNA-cleaving activity was observed for all compounds tested, mimics I,III, and V bearing an intercalative moiety along with the primary amine and/or imidazole moieties exhibited potent RNA-cleaving activity at near physiological pH. The RNA-cleaving reactions of the compounds show characteristic bell-shaped pH dependency, and the optimal pH values for III and V were well correlated to the pK _a values of their active sites, primary amine, and imidazole moieties.

ACKNOWLEDGMENTS

A part of this work was financially supported by a Grant-in-Aid for Scientific Research from the Ministry of Education Japan.

Notes

^*Takagi et al. reported the cleavage of double-stranded DNA by a Cu(II) complex of polyamine-linked DNA-intercalator¹ which is an analogous compound of mimic I. We have also ovserved a cleavage of pBR322 DNA by mimic I under the presence of an equal amount of Cu(II) ion. The magnitude of the cleavage was, however, modest to low in our results (data not shown).

^*A recent report of Ushijima et al. describes a site-specific clevage tRNA mediated by β-oligoDNA functionalized at the 5′-terminus with polyamine derivatives²⁶ which are essentially same as mimic I and III described in this article.