The contribution of adenines in the catalytic core of 10-23 DNAzyme improved by the 6-amino group modifications.

In the catalytic core of 10-23 DNAzyme, its five adenine residues are moderate conservative, but with highly conserved functional groups like 6-amino group and 7-nitrogen atom. It is this critical conservation that these two groups could be modified for better contribution. With 2'-deoxyadenosine analogues, several functional groups were introduced at the 6-amino group of the five adenine residues. 3-Aminopropyl substituent at 6-amino group of A15 resulted in a five-fold increase of kobs. More efficient DNAzymes are expected by delicate design of the linkage and the external functional groups for this 6-amino group of A15. With this modification approach, other functional groups or residues could be optimized for 10-23 DNAzyme.

Position-specific modification with imidazolyl group on10-23 DNAzyme realized catalytic activity enhancement.

Nucleoside analogues with imidazolyl and histidinyl groups were synthesized for site-specific modification on the catalytic core of 10-23 DNAzyme. The distinct position-dependent effect of imidazolyl group was observed. Positive effect at A9 position was always observed. The pH- and Mg(2+)-dependence of the imidazolyl-modified DNAzymes suggested that imidazolyl group in 10-23 DNAzyme probably plays a dual role, its hydrogen bonding ability and spacial occupation play the favorable influence on the catalytic conformation of the modified DNAzymes. This research demonstrated that the catalytic performance of DNAzymes could be enhanced by incorporation of additional functional groups. Chemical modification is a feasible approach toward more efficient DNAzymes for therapeutic and biotechnological applications.