Nucleic Acids Research Advance Access published online on December 2, 2008
Nucleic Acids Research, doi:10.1093/nar/gkn930
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DNAzyme-mediated catalysis with only guanosine and cytidine nucleotides
1Department of Biochemistry and Biomedical Sciences and 2Department of Chemistry, McMaster University, Hamilton, Ontario, Canada L8N 3Z5
*To whom correspondence should be addressed. Tel: +1 905 525 9140. Ext. 22462; Fax: +1 905 522 9033; Email: liying{at}mcmaster.ca
Received September 7, 2008. Revised November 3, 2008. Accepted November 4, 2008.
Single-stranded DNA molecules have the capacity to adopt catalytically active structures known as DNAzymes, although the fundamental limits of this ability have not been determined. Starting with a parent DNAzyme composed of all four types of standard nucleotides, we conducted a search of the surrounding sequence space to identify functional derivatives with catalytic cores composed of only three, and subsequently only two types of nucleotides. We provide the first report of a DNAzyme that contains only guanosine and cytidine deoxyribonucleotides in its catalytic domain, which consists of just 13 nucleotides. This DNAzyme catalyzes the Mn2+-dependent cleavage of an RNA phosphodiester bond
5300-fold faster than the corresponding uncatalyzed reaction, but
10 000-fold slower than the parent. The demonstration of a catalytic DNA molecule made from a binary nucleotide alphabet broadens our understanding of the fundamental limits of nucleic-acid-mediated catalysis.
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