@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 {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.}
}
