Chemical Ribonucleases: VII. Effect of Positively Charged RNA-Binding Domains and Hydrophobic Fragments of the Conjugates Based on 1,4-Diazabicyclo[2.2.2]Octane and Imidazole on Their Ribonuclease Activity

N.†V.†Tamkovich1, A.†V.†Malyshev1, D.†A.†Konevetz1, V.†N.†Silínikov1, M.†A.†Zenkova1†# and V.†V.†Vlassov1

#Phone: (383) 333-37-61; fax: (383) 333-36-77; e-mail: marzen@niboch.nsc.ru

1Institute of Chemical Biology and Fundamental Medicine, Siberian Division, Russian Academy of Sciences, pr. Akademika Lavrentíeva 8, Novosibirsk, 630090, Russia

Received: May†16,†2006; in final form: June†9,†2006

Abstract.††The effect of the total positive charge in the RNA-binding domain of chemical ribonucleases that are conjugates of bisquaternary salts of 1,4-diazabicylo[2.2.2]octane and imidazole on the cleavage of an HIV-1 RNA fragment was studied. An increase in the positive charge from +2 to +4 was shown to result in a significant growth in the ribonuclease activity. Possible mechanisms of the interactions between structural moieties of chemical ribonucleases and RNA that enable an effective catalysis of the cleavage of phosphodiester bonds are discussed.

Key words:††artificial ribonucleases,†1,4-diazabicyclo[2.2.2]octane,†RNA,†RNA cleavage

Russian Journal of Bioorganic Chemistry 2007, 33 (2): 233-242