Abstract

In the 15-mer catalytic core of 10-23 DNAzyme, each residue contributes to the catalytic conformation differently. Here, the critically conserved T4 and the least conserved T8 were modified on their 5-position with hydroxyl, imidazolyl, and amino groups with a hydrogen-bonding ability. These external functional groups induced new interactions within the catalytic core, resulting in both negative and positive effects on the catalytic activity of 10-23 DNAzyme, and the different linkages could be used to modulate the effect of the functional groups. The conservation of T4 and T8 could be recognized at the level of the nucleobase, but at the level of the functional group, T4 is not completely conserved. Their 5-methyl groups could be modified for a better performance in terms of the DNAzyme.

Highlights

  • In the 15-mer catalytic core of 10-23 DNAzyme, each residue contributes to the catalytic conformation differently

  • It could not be concluded that any residues or functional groups are directly involved in the catalytic reaction, but the importance of each nucleotide has been recognized by these screening approaches

  • In the complex tertiary structure of the catalytic core of 10-23 DNAzyme, the functional groups around each nucleobase are supposed to play an active role in forming the catalytic conformation, in addition to the base stacking interaction

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Summary

Introduction

In the 15-mer catalytic core of 10-23 DNAzyme, each residue contributes to the catalytic conformation differently. The critically conserved T4 and the least conserved T8 were modified on their 5-position with hydroxyl, imidazolyl, and amino groups with a hydrogen-bonding ability These external functional groups induced new interactions within the catalytic core, resulting in both negative and positive effects on the catalytic activity of 10-23 DNAzyme, and the different linkages could be used to modulate the effect of the functional groups. Its catalytic cleaving ability on complementary RNA has attracted much attention, from practical therapeutics [2,3,4] to catalytic mechanism studies [5,6] It is an ideal model for studying the artificial functions and related tertiary structures of DNA molecules of non-genetic carriers, especially when no counterpart of DNAzyme has yet been found in nature. T4 is always negatively affected by these modifications

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