@article {2438,
	title = {A DNAzyme with Three Protein-Like Functional Groups: Enhancing Catalytic Efficiency of M2+-Independent RNA Cleavage},
	journal = {Chembiochem},
	volume = {10},
	number = {12},
	year = {2009},
	note = {ISI Document Delivery No.: 487MWTimes Cited: 5Cited Reference Count: 76Hollenstein, Marcel Hipolito, Christopher J. Lam, Curtis H. Perrin, David M.},
	month = {Aug},
	pages = {1988-1992},
	type = {Article},
	keywords = {BEACON SENSOR, biology, CLEAVING DNA ENZYME, CYTOSOLIC FREE MAGNESIUM, DEOXYRIBOZYMES, DNAzymes, enzyme catalysis, EVOLUTION, HAIRPIN RIBOZYME, HIGH-DENSITY, IN-VITRO SELECTION, ION, nucleic acids, NUCLEIC-ACIDS, RNAse A mimics, synthetic},
	isbn = {1439-4227},
	url = {<Go to ISI>://000269279700012},
	author = {Hollenstein, M. and Hipolito, C. J. and Lam, C. H. and Perrin,David M.}
}
@article {2636,
	title = {Investigation of the Catalytic Mechanism of a Synthetic DNAzyme with Protein-like Functionality: An RNaseA Mimic?},
	journal = {Journal of the American Chemical Society},
	volume = {131},
	number = {15},
	year = {2009},
	note = {ISI Document Delivery No.: 434IJTimes Cited: 3Cited Reference Count: 108Thomas, Jason M. Yoon, Jung-Ki Perrin, David M.},
	month = {Apr},
	pages = {5648-5658},
	type = {Article},
	abstract = {The protein enzyme ribonuclease A (RNaseA) cleaves RNA with catalytic perfection, although with little sequence specificity, by a divalent metal ion (M2+)-independent mechanism in which a pair of imidazoles provides general acid and base catalysis, while a cationic amine provides electrostatic stabilization of the transition state. Synthetic imitation of this remarkable organo-catalyst ("RNaseA mimicry") has been a longstanding goal in biomimetic chemistry. The 9(25)-11 DNAzyme contains synthetically modified nucleotides presenting both imidazole and cationic amine side chains, and catalyzes RNA cleavage with turnover in the absence of M2+ similarly to RNaseA. Nevertheless, the catalytic roles, if any, of the "proteinlike" functional groups have not been defined, and hence the question remains whether 925-11 engages any of these functionalities to mimic aspects of the mechanism of RNaseA. To address this question, we report a mechanistic investigation Of 925-11 Catalysis wherein we have employed a variety of experiments, such as DNAzyme functional group deletion, mechanism-based affinity labeling, and bridging and nonbridging phosphorothioate substitution of the scissile phosphate. Several striking parallels exist between the results presented here for 925-11 and the results of analogous experiments applied previously to RNaseA. Specifically, our results implicate two particular imidazoles in general acid and base catalysis and suggest that a specific cationic amine stabilizes the transition state via diastereoselective interaction with the scissile phosphate. Overall, 925-11 appears to meet the minimal criteria of an RNaseA mimic; this demonstrates how added synthetic functionality can expand the mechanistic repertoire available to a synthetic DNA-based catalyst.},
	keywords = {ACID-BASE CATALYSIS, CLEAVING DNA ENZYME, COMPLEX, CYTOSOLIC FREE MAGNESIUM, DELTA VIRUS RIBOZYME, DINUCLEAR ZN(II), DIVALENT METAL-IONS, HAIRPIN RIBOZYME CATALYSIS, HDV GENOMIC, IN-VITRO SELECTION, RIBONUCLEASE-A, RIBOZYME},
	isbn = {0002-7863},
	url = {<Go to ISI>://000265268100049},
	author = {Thomas, J. M. and Yoon, J. K. and Perrin,David M.}
}
@article {2137,
	title = {Synthesis and Enzymatic Incorporation of Modified Deoxyadenosine Triphosphates},
	journal = {European Journal of Organic Chemistry},
	number = {29},
	year = {2008},
	note = {ISI Document Delivery No.: 365YXTimes Cited: 7Cited Reference Count: 35Lam, Curtis Hipolito, Christopher Perrin, David M.},
	month = {Oct},
	pages = {4915-4923},
	type = {Article},
	abstract = {Several deoxyadenosine triphosphates containing modifications at the 8-position have been synthesized. Suitably protected 8-bromodeoxyadenosines were coupled with five imidazole-containing moieties by nucleophilic aromatic substitution or Sonagashira coupling to give modified nucleosides that were then triphosphorylated. Incorporation assays were performed for these modified residues with many commercially available DNA polymerases, and it was found that two of the modified dATPs could be effectively taken up as substrates by Sequenase V2.0. These two residues are candidates for substrates in combinatorial selections in the search for improved catalysis from DNAzymes. ((C) Wiley-VCH Verlag GmbH \& Co. KGaA, 69451 Weinheim, Germany, 2008)},
	keywords = {AMINO-ACID, bioorganic chemistry, CATALYTIC REPERTOIRE, CLEAVING DNA ENZYME, DERIVATIVES, DNA, ENZYMES, FUNCTIONALITIES, HETEROCYCLES, IN-VITRO SELECTION, NUCLEIC-ACIDS, nucleotides, OLIGONUCLEOTIDES, PCR, POLYMERASES, SELEX},
	isbn = {1434-193X},
	url = {<Go to ISI>://000260447200009},
	author = {Lam, C. and Hipolito, C. and Perrin,David M.}
}
@article {1007,
	title = {High affinity DNAzyme-based ligands for transition metal cations - a prototype sensor for Hg2+},
	journal = {Organic \& Biomolecular Chemistry},
	volume = {2},
	number = {3},
	year = {2004},
	note = {ISI Document Delivery No.: 776YCTimes Cited: 32Cited Reference Count: 47},
	month = {Feb},
	pages = {307-312},
	type = {Article},
	abstract = {Inspired by recent interest in DNAzymes as transition metal ion sensors, a survey of the effects of various transition metals on the intramolecular cleavage rate of an imidazole modified, M2+-independent, self-cleaving "9(25)-11" DNA is reported. In particular, 9(25)-11 activity was strongly inhibited by Hg2+ (K-d(APP) = 110 +/- 9 nM). It is postulated that the affinity and selectivity of 9(25)-11 for Hg2+ stems from the fact that this synthetically modified DNAzyme contains imidazoles. This study demonstrates the utility of modified nucleotides in developing DNAzyme sensors for metals ions, especially those for which unmodified nucleic acids might not serve as inherently good ligands.},
	keywords = {2-STEP MECHANISM, BIOSENSOR, CATALYTIC REPERTOIRE, CLEAVING DNA ENZYME, IMIDAZOLYL FUNCTIONALITIES, MERCURIC ION, MERCURY(II), NUCLEIC-ACIDS, NUCLEOSIDES, SELECTION},
	isbn = {1477-0520},
	url = {<Go to ISI>://000189146100008},
	author = {Thomas, J. M. and Ting, R. and Perrin,David M.}
}
@article {1016,
	title = {Selection and characterization of DNAzymes with synthetically appended functionalities: A case of a synthetic RNaseA mimic},
	journal = {Pure and Applied Chemistry},
	volume = {76},
	number = {7-8},
	year = {2004},
	note = {ISI Document Delivery No.: 855WQTimes Cited: 1Cited Reference Count: 7039th IUPAC Congress/86th Conference of the Canadian-Society-for-ChemistryAUG 10-15, 2003Ottawa, CANADACanadian Soc Chem, Natl Res Council Canada, Int Union Pure \& Appl Chem},
	month = {Jul-Aug},
	pages = {1571-1577},
	type = {Proceedings Paper},
	abstract = {We have been interested in merging synthetic nucleotide chemistry with combinatorial selection of DNAzymes to deliver a more complete (and complex) chemical complement to the catalytic repertoire of nucleic acids. Thus we ask, what do modified dNTPs really bring to nucleic acids in terms of an increased repertoire? In asking this question, we have looked first at conditions, and more recently for reaction classes where nucleic acids are found to be catalytically inefficient, deficient, or at least to date, seemingly incapable of certain functions. A case of this is M2+-independent ribophosphodiester hydrolysis at physiological pH and low ionic strength where nucleic acids exhibit especially low rate constants for self-cleavage and seem to be incapable of turnover.},
	keywords = {CATALYTIC, CLEAVING DNA ENZYME, DIVALENT METAL-ION, IMIDAZOLYL FUNCTIONALITIES, IN-VITRO SELECTION, MONOVALENT CATIONS, NUCLEIC-ACIDS, NUCLEOSIDE 5{\textquoteright}-TRIPHOSPHATES, REPERTOIRE, SEQUENCE-SPECIFIC CLEAVAGE, SITE-SPECIFIC CLEAVAGE},
	isbn = {0033-4545},
	url = {<Go to ISI>://000224006000028},
	author = {Ting, R. and Lermer, L. and Thomas, J. and Roupioz, Y. and Perrin,David M.}
}
@article {1017,
	title = {Substrate specificity and kinetic framework of a DNAzyme with an expanded chemical repertoire: a putative RNaseA mimic that catalyzes RNA hydrolysis independent of a divalent metal cation},
	journal = {Nucleic Acids Research},
	volume = {32},
	number = {22},
	year = {2004},
	note = {ISI Document Delivery No.: 887METimes Cited: 24Cited Reference Count: 71},
	pages = {6660-6672},
	type = {Article},
	abstract = {This work addresses the binding, cleavage and dissociation rates for the substrate and products of a synthetic RNaseA mimic that was combinatorially selected using chemically modified nucleoside triphosphates. This trans-cleaving DNAzyme, 9(25)-11t, catalyzes sequence-specific ribophosphodiester hydrolysis in the total absence of a divalent metal cation, and in low ionic strength at pH 7.5 and in the presence of EDTA. It is the first such sequence capable of multiple turnover. 9(25)-11t consists of 31 bases, 18 of which form a catalytic domain containing 4 imidazole and 6 allylamino modified nucleotides. This sequence cleaves the 15 nt long substrate, S1, at one embedded ribocytosine at the eighth position to give a 5{\textquoteright}-product terminating in a 2{\textquoteright},3{\textquoteright}-phosphodiester and a 3{\textquoteright}-product terminating in a 5{\textquoteright}-OH. Under single turnover conditions at 24degreesC, 9(25)-11t displays a maximum first-order rate constant, k(cat), of 0.037 min(-1) and a catalytic efficiency, k(cat)/K-m, of 5.3 x 10(5) M-1 min(-1). The measured value of k(cat) under catalyst excess conditions agrees with the value of k(cat) observed for steady-state multiple turnover, implying that slow product release is not rate limiting with respect to multiple turnover. The substrate specificity of 9(25)-11t was gauged in terms of k(cat) values for substrate sequence variants. Base substitutions on the scissile ribose and at the two bases immediately downstream decrease k(cat) values by a factor of 4 to 250, indicating that 9(25)-11t displays significant sequence specificity despite the lack of an apparent Watson-Crick base-pairing scheme for recognition.},
	keywords = {CATIONS, CLEAVING DNA ENZYME, CYTOSOLIC FREE MAGNESIUM, HAIRPIN RIBOZYME CLEAVAGE, HAMMERHEAD, IMIDAZOLYL FUNCTIONALITIES, IN-VITRO SELECTION, MONOVALENT, NUCLEIC-ACIDS, NUCLEOSIDE TRIPHOSPHATES, SEQUENCE-SPECIFIC CLEAVAGE},
	isbn = {0305-1048},
	url = {<Go to ISI>://000226309400036},
	author = {Ting, R. and Thomas, J. M. and Lermer, L. and Perrin,David M.}
}
@article {430,
	title = {Toward an RNaseA mimic: a DNAzyme with imidazoles and cationic amines},
	journal = {Journal of the American Chemical Society},
	volume = {124},
	number = {34},
	year = {2002},
	note = {ISI Document Delivery No.: 586GJTimes Cited: 41Cited Reference Count: 52},
	month = {Aug},
	pages = {9960-9961},
	type = {Article},
	keywords = {CATALYTIC REPERTOIRE, CATIONS, CLEAVING DNA ENZYME, FUNCTIONALITIES, HAMMERHEAD, IN-VITRO SELECTION, MONOVALENT, NUCLEIC-ACIDS, RIBOZYME, SEQUENCE-SPECIFIC CLEAVAGE, SITE-SPECIFIC CLEAVAGE},
	isbn = {0002-7863},
	url = {<Go to ISI>://000177576000001},
	author = {Lermer, L. and Roupioz, Y. and Ting, R. and Perrin,David M.}
}
@article {5161,
	title = {Bridging the gap between proteins and nucleic acids: A metal-independent RNAseA mimic with two protein-like functionalities},
	journal = {Journal of the American Chemical Society},
	volume = {123},
	number = {8},
	year = {2001},
	note = {ISI Document Delivery No.: 405LXTimes Cited: 74Cited Reference Count: 49},
	month = {Feb},
	pages = {1556-1563},
	type = {Article},
	abstract = {Two synthetically modified nucleoside triphosphate analogues (adenosine modified with an imidazole and uridine modified with a cationic amine) are enzymatically polymerized in tandem along a degenerate DNA library for the combinatorial selection of an RNAse A mimic. The selected activity is consistent with both electrostatic and general acid/base catalysis at physiological pH in the absence of divalent metal cations. The simultaneous use of two modified nucleotides to enrich the catalytic repertoire of DNA-based catalysts has never before been demonstrated and evidence of general acid/base catalysis at pH 7.4 for a DNAzyme has never been previously observed in the absence of a divalent metal cation or added cofactor, This work illustrates how the incorporation of protein-like functionalities in nucleic acids can bridge the gap between proteins and oligonucleotides underscoring the potential for using nucleic acid scaffolds in the development of new materials and improved catalysts for use in chemistry and medicine.},
	keywords = {5{\textquoteright}-TRIPHOSPHATES, ADENOSINE, ANALOG, CATALYSIS, CLEAVAGE, CLEAVING DNA ENZYME, DERIVATIVES, IN-VITRO SELECTION, PHOSPHORYL-TRANSFER-REACTIONS, PORPHYRIN METALATION, TRANSITION-STATE},
	isbn = {0002-7863},
	url = {<Go to ISI>://000167162100002},
	author = {Perrin,David M. and Garestier, T. and Helene, C.}
}
