Ribozyme mimics as catalytic antisense reagents

Bashkin, James K.; Sampath, UmaShanker; Frolova, Elena I.

doi:10.1007/bf02787910

Cited by 18 publications

(20 citation statements)

References 47 publications

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“…The chimeric ribo/2Ј-O-methylribooligonucleotides (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) were synthesised from commercial 2Ј-O-methylated (Glenn Research) and 2Ј-O-[1-(2-fluorophenyl)-4-methoxypiperidin-4-yl] (2Ј-O-Fpmp) protected (Cruachem) building blocks by a conventional phosphoramidite strategy, according to the standard RNA-coupling protocol of ABI 392 DNA/RNA Synthesizer. The protecting groups were removed and the crude oligonucleotides were purified as described previously.…”

Section: Methodsmentioning

confidence: 99%

“…The development of sequence-selective RNA cleaving reagents, artificial RNases, has attracted considerable attention over the last decade. [1][2][3][4][5][6] It is hoped that these cleaving agents will offer novel methods to treat viral infections, cancer, hereditary diseases or antibiotic-resistant bacterial infections. The general concept for the design of such agents is simple: an oligonucleotide recognises the target RNA sequence by hybridisation and its catalytically active function, once attached, induces a chemical modification that inactivates the target molecule.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The cleavage of phosphodiester bonds within small RNA bulges in the presence and absence of metal ion catalysts †

Kaukinen

Bielecki

Mikkola

et al. 2001

J. Chem. Soc., Perkin Trans. 2

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This work studies the effect of RNA structure on the reactivity of RNA phosphodiester bonds. The aim of the study is to evaluate those structural parameters that affect reactivity to support the development of sequence-specific RNA cleaving agents. The cleavage of phosphodiester bonds within one-to five-nucleotide bulges has been studied in buffer solutions (pH 8.4), and in the presence of Zn 2ϩ aqua ion (pH 6.4) or its 1,5,9-triazacyclododecane complex (pH 7.4). Molecular modelling has been applied to study the structure of the substrates. The basis of the reactivity and the catalytic potential of metal ion-based cleaving agents are discussed.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The cleavage of phosphodiester bonds within small RNA bulges in the presence and absence of metal ion catalysts †

Kaukinen

Bielecki

Mikkola

et al. 2001

J. Chem. Soc., Perkin Trans. 2

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“…Arti®cial hydrolases based on main-group, lanthanide or transition metal complexes have been developed as nonenzymatic alternatives for the hydrolysis of the phosphodiester bonds in DNA and RNA (Chin, 1991;Kim & Suh, 1994;Williams & Chin, 1996;Williams et al, 1999). It has been suggested that such catalysts may have a signi®cant future impact in gene-cloning, gene-mapping, or therapeutics (Bashkin et al, 1995;Komiyama & Sumaoka, 1996;Hegg & Burstyn, 1998;Komiyama et al, 1999). Cobalt(III), with its high charge density, is a potent candidate for use in hydrolysing phosphodiesters; for example, recently published values for DNA cleavage show that Co III complexes have rate constants of around 2 Â 10 4 s À1 , which is about three times higher than that for europium(III) salts (Hettich & Schneider, 1997).…”

Section: Commentmentioning

confidence: 99%

Dichloro{methyl 4-[(1,4,7,10-tetraazacyclododec-1-yl)methyl]benzoate}cobalt(III) methylsulfate

et al. 2003

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“…Catalytic RNA is also a very good method for development of specific catalysts within its limited substrate range. Clever applications of specific RNA hydrolysis are currently being applied to medical problems (93)(94)(95). By contrast, the de novo techniques have yielded few breakthroughs of practical value.…”

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confidence: 99%

On the failure of de novo-designed peptides as biocatalysts.

Corey

1996

Proc. Natl. Acad. Sci. U.S.A.

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While the elegance and efficiency of enzymatic catalysis have long tempted chemists and biochemists with reductionist leanings to try to mimic the functions of natural enzymes in much smaller peptides, such efforts have only rarely produced catalysts with biologically interesting properties. However, the advent of genetic engineering and hybridoma technology and the discovery ofcatalytic RNA have led to new and very promising alternative means of biocatalyst development. Synthetic chemists have also had some success in creating nonpeptide catalysts with certain enzyme-like characteristics, although their rates and specificities are generally much poorer than those exhibited by the best novel biocatalysts based on natural structures. A comparison of the various approaches from theoretical and practical viewpoints is presented. It is suggested that, given our current level of understanding, the most fruitful methods may incorporate both iterative selection strategies and rationally chosen small perturbations, superimposed on frameworks designed by nature.A thorough understanding of the chemical and structural bases of biological catalysis would lead to advances in medicine, synthetic chemistry, materials science, agriculture, and other fields. Such a level of insight, when it exists, will likely be signaled by a clear demonstration of the ability to construct, from first principles, a range of catalysts capable of transmuting both biopolymers and small molecules to desired products with high specificity and acceptable efficiency. The specialized proteins known as enzymes are the molecules that usually fill this role in nature, and the most likely means by which we could achieve the objective of catalysis to specification is by attaining an understanding of enzyme structure and function sufficient to allow design and construction of new molecules based on the same principles. This degree of understanding has been elusive, and there is as yet no case of an protein or peptide designed de novo that catalyzes a reaction of biological interest with efficiency and specificity comparable to that of natural enzymes or a novel reaction not carried out by enzymes. However, competing strategies of developing novel biocatalysts which make use of the frameworks of natural proteins have enjoyed considerable success in catalyzing both transformations analogous to the cognate reactions of natural enzymes and, in some cases, entirely novel reactions. The two major techniques in this category are catalytic antibodies (refs. 1 and 2; for a recent review, see ref.3) and reengineered natural enzymes (RNEs; for reviews, see refs. 4 and 5). Catalytic antibodies, which were originally reported in 1986, can be characterized as antibodies directed against haptens, which are usually synthetic analogs of the transition states of the chemical reactions to be catalyzed. Reengineering of enzymes has been possible in principle since the advent of genetic engineering, more than two decades ago; a review of Medline entries indicated that st...

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Ribozyme mimics as catalytic antisense reagents

Cited by 18 publications

References 47 publications

The cleavage of phosphodiester bonds within small RNA bulges in the presence and absence of metal ion catalysts †

The cleavage of phosphodiester bonds within small RNA bulges in the presence and absence of metal ion catalysts †

Dichloro{methyl 4-[(1,4,7,10-tetraazacyclododec-1-yl)methyl]benzoate}cobalt(III) methylsulfate

On the failure of de novo-designed peptides as biocatalysts.

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