A structure-activity relationship study for 2'-deoxyadenosine analogs at A9 position in the catalytic core of 10-23 DNAzyme for rate enhancement.

Qi Wang, Di Zhang, Yang Liu, Maosheng Cheng, Junlin He, Keliang Liu

Nucleic acid therapeutics 2012 Dec

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Modification on the catalytic core of 10-23 DNAzyme with protein-like functional groups is a potential approach to obtain its more efficient analogs. In our efforts for this purpose, a lead structure (DZ-2-9) with 8-aza-7-deaza-2'-deoxyadenosine at the A9 position in its catalytic core was obtained. Here we report our structure-activity relationship studies on this lead structure. Various functional groups of different chemical properties were introduced through the 7-substituents of 8-aza-7-deaza-2'-deoxyadenosine to DZ-2-9. The functional groups capable of forming hydrogen bonds, like amino and hydroxyl groups, are more favorable for catalytic rate enhancement than the large groups with spacial occupation, like phenyl and tert-butylphenyl groups, and the flexible alkyl linkage was the more preferred choice for optimizing their positive effect. Furthermore, they exerted positive effect cooperatively with the N8 atom. These results give us a clear hint in the design of compounds for A9 substitution of 10-23 DNAzyme for more efficient DNAzymes.

Citation

Qi Wang, Di Zhang, Yang Liu, Maosheng Cheng, Junlin He, Keliang Liu. A structure-activity relationship study for 2'-deoxyadenosine analogs at A9 position in the catalytic core of 10-23 DNAzyme for rate enhancement. Nucleic acid therapeutics. 2012 Dec;22(6):423-7