@article {2285,
	title = {Probing General Base Catalysis in the Hammerhead Ribozyme},
	journal = {Journal of the American Chemical Society},
	volume = {130},
	number = {46},
	year = {2008},
	note = {ISI Document Delivery No.: 406QZTimes Cited: 8Cited Reference Count: 53Thomas, Jason M. Perrin, David M.},
	month = {Nov},
	pages = {15467-15475},
	type = {Article},
	abstract = {Recent structural and computational studies have shed new light on the catalytic mechanism and active site structure of the RNA cleaving hammerhead ribozyme. Consequently, specific ribozyme functional groups have been hypothesized to be directly involved in general/acid base catalysis. In order to test this hypothesis, we have developed an affinity label to identify the functional general base in the S. mansoni hammerhead ribozyme. The ribozyme was reacted with a substrate analogue bearing a 2{\textquoteright}-bromoacetamide group in place of the nucleophilic 2{\textquoteright}-hydroxyl group which would normally be deprotonated by a general base. The electrophilic 2{\textquoteright}-bromoacetamide group is poised to alkylate the general base, which is subsequently identified by footprinting analysis. Herein, we demonstrate alkylation of N1 of G12 in the hammerhead ribozyme in a pH and [Mg2+] dependent manner that is consistent with the native cleavage reaction. These results provide substantial evidence that deprotonated N1 of G12 functions directly as a general base in the hammerhead ribozyme; moreover, our experiments provide evidence that the pK(a) of G12 is perturbed downward in the context of the active site structure. We also observed other pH-independent alkylations, which do not appear to reflect the catalytic mechanism, but offer further insight into ribozyme conformation and structure.},
	keywords = {ACTIVE-SITE, CLEAVAGE, CRYSTAL-STRUCTURE, DELTA VIRUS RIBOZYME, HAIRPIN RIBOZYME, MECHANISM, METAL-ION, MONOVALENT CATIONS, NUCLEOBASE CATALYSIS, RNA},
	isbn = {0002-7863},
	url = {<Go to ISI>://000263311300051},
	author = {Thomas, J. M. 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.}
}
