DNAmoreDB - A Database of Deoxyribozymes

Published on 2012 in Chemical Science issue 5.

DOI:10.1039/C2SC01067D

Abstract:

We report that micromolar concentrations of lanthanide ions can be required cofactors for DNA-hydrolyzing deoxyribozymes. Previous work identified deoxyribozymes that simultaneously require both Zn2+ and Mn2+ to achieve DNA-catalyzed DNA hydrolysis (1012 rate enhancement); a mutant of one such DNA catalyst requires only Zn2+. Here we show that in vitro selection in the presence of 10 μM lanthanide ion (Ce3+, Eu3+, or Yb3+) along with 1 mM Zn2+ leads to numerous DNA-hydrolyzing deoxyribozymes that strictly require the lanthanide ion as well as Zn2+ for catalytic activity. These DNA catalysts have a range of lanthanide dependences, including some deoxyribozymes that strongly favor one particular lanthanide ion (e.g., Ce3+ ≫ Eu3+ ≫ Yb3+) and others that function well with more than one lanthanide ion. Intriguingly, two of the Yb3+-dependent deoxyribozymes function well with Yb3+ alone (Kd,app ∼ 10 μM, in the absence of Zn2+) and have little or no activity with Eu3+ or Ce3+. In contrast to these selection outcomes when lanthanide ions were present, new selections with Zn2+ or Mn2+ alone, or Zn2+ with Mg2+/Ca2+, led primarily to deoxyribozymes that cleave DNA by deglycosylation and β-elimination rather than by hydrolysis, including several instances of depyrimidination. We conclude that lanthanide ions warrant closer attention as cofactors when identifying new nucleic acid catalysts, especially for applications in which high concentrations of polyvalent metal ion cofactors are undesirable.



DNAzymes linked to this article:

Name Isolated sequence Length Reaction
6YF15 GTCGCAGCCCGACGGGGTCTACCGGAGTGCATGTGGCGGG      40 DNA cleavage
6YF27 CCCAGATCGGCAACGGGTCGTTCACGATGCCTACGAGGGT      40 DNA cleavage
8YG1 CTCCCCGACCAACGAGCCTAGGGGTACATTCTTAGGTGGC      40 DNA cleavage
8YG7 CCGGCGCGCCAAGGTGCTTAAAACGCATCCGTATACGCAA      40 DNA cleavage
8YG24 GAGCAGGTAGGATGAGCACCGCCCGAAATGAATATGCCGG      40 DNA cleavage
8YG29 ACGCAAGTCCCCTGTCGTCAATGGGGCGGACCGCACATTT      40 DNA cleavage
8YG11       0 DNA cleavage
6YF2 CCCACACCATATACAAGGGAAGATGGGGCGTCCGAGGGCT      40 DNA cleavage
6YF13 AAGCCGGAATAGCCGATGAGGCGCCAGAGAAGTCCCCCGT      40 DNA cleavage
6YF16 CCCACCTCAAATGTTGTATGAGCAAGAGACGTCCGAGGGT      40 DNA cleavage
6YF20 CCCACTGTGCCAATGCGCCATGGCAACAACGTCCGAGGGC      40 DNA cleavage
6YJ10 CGCAGCGGGGTGAAACGCGGTGAGAACTCGAATGTCGTTT      40 DNA cleavage
6YJ14 GTGGTACGGGGTGTAGTAGGCACGACGCCCTGCTCCATGG      40 DNA cleavage
7YK24 GCGAGGGGCAAGCGCGAGAACCATGATACTCGCGACTAAG      40 DNA cleavage
7YK34 CCCCCGGTCATGGGTCAAGCAGAGCGAGGAGAATGAAAGG      40 DNA cleavage
7YK35 CCCCCGCAAAGAGAAGCAAGGGGGACCGCTTTGAATACGG      40 DNA cleavage
6YL4 TGGGGGCTAGCCGAGAGCAAAGCCATGCAAAACGAGGACC      40 DNA cleavage
6YL11 GCAGGCGAGTACGGCACAACAGACCTATACAACTAGGTCC      40 DNA cleavage
6YL24 CAAGGGTCCAACAGCCAGGTCAAGTTGCCCGCAGCTGGCC      40 DNA cleavage
6YL34 GCAGGCGAGCACGGCATGAAAAGAATGTTAATACCATTCT      40 DNA cleavage
8YM4 TAGAGAGCCCAGGAATTAGTCAGTCCCGGGTTACGAAAAG      40 DNA cleavage
8YM17 AAGTGTACGGATGCCCCCTGCGCCTCGGTCAAATGTAGGC      40 DNA cleavage
8YM20 AACCGTGGCAGCAGATCCTCAAGCGGGGAAGACAGCAGTA      40 DNA cleavage
8YM26 AAGCCAGATGTATTCCTCCTACCGCGGACCGAGGATGGGA      40 DNA cleavage
7YE2 CCCCGTCCGCCCCTGAATTCCGCAGATTGGGGATTACTGA      40 DNA cleavage
7YE5 CAGACGTGCGATCGGATCAAGTCGCTCGAGAAGTCCCCCG      40 DNA cleavage
7YE8 CCAATCCAAGTACAATTGGATGTCCAGAGAAGTCCCCCGA      40 DNA cleavage
7YE11       0 DNA cleavage
7YE19 CAGCGAGACACGTAGTGATCGGCGCTCGAGAAGTCCCCCG      40 DNA cleavage
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