In vitro selection of RNA lectins: using combinatorial chemistry to interpret ribozyme evolution

Lato, Susan M.; Boles, Amy R.; Ellington, Andrew D.

doi:10.1016/1074-5521(95)90048-9

Cited by 117 publications

(79 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The sequences reported for these RNA aptamers generally do not resemble the DNA G-rich sequences we have identified in this selection, although a subset in one study did have short G-rich sections (22). It is possible that the use of DNA in the present study restricted the structural motifs more than when RNA is used.…”

Section: ϫ7mentioning

confidence: 57%

DNA ligands that bind tightly and selectively to cellobiose

Yang

Goldstein

Mei

et al. 1998

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

106

View full text Add to dashboard Cite

Cell surface oligosaccharides have been shown to play essential biological roles in such diverse biological phenomena as cellular adhesion, molecular recognition, and inflammatory response. The development of high-affinity ligands capable of selectively recognizing a variety of small motifs in different oligosaccharides would be of significant interest as experimental and diagnostic tools. As a step toward this goal we have developed DNA ligands that recognize the disaccharide cellobiose, whether in soluble form or as the repeating unit of the polymer, cellulose. These DNA ''aptamers'' bind with high selectivity to cellobiose with little or no affinity for the related disaccharides lactose, maltose, and gentiobiose. Thus, the DNA ligands can discriminate sugar epimers, anomers, and disaccharide linkages.Oligosaccharide antigens play essential biological roles in cellular adhesion, molecular recognition, and inflammatory response. Classical carbohydrate binding macromolecules are proteins. These include plant and animal lectins (1-3) and anticarbohydrate antibodies raised in animals and humans (4). The ability to discriminate the presence of different saccharide types with relatively subtle structural differences would be of benefit in both experimental applications and diagnostics. Many routine clinical screens and research applications use immunological methods for which there are currently no antibodies that can discriminate among similar sugar linkages. Possible applications for selective, high-affinity ligands include Western blots, in situ staining, ''immuno'' precipitation, and various types of ''immuno'' affinity in microtiter format.High-affinity nucleic acid ligands, termed ''aptamers,'' can be selected from a random pool of nucleic acid sequences (refs. 5-12, reviewed in refs. 13-15). Aptamer selection is in theory much faster, cheaper, more versatile, and more reliable than antibody preparation. Such selection produces high-affinity ligands that can be propagated indefinitely with little risk of losing the stock, significantly lower cost than antibodies, and completely obviates the use of animals. In addition to possible ethical considerations, this also provides the opportunity to generate ligands to antigens that are toxic to humans and animals. The selection procedure, termed SELEX (systemic evolution of ligands by exponential enrichment, ref. 7) involves the iterative isolation of ligands out of the random sequence pool with affinity for a defined target molecule and PCR-based amplification of the selected RNA or DNA oligonucleotides after each round of isolation. This previously has been suggested as a route to drug discovery (7), with the possible use of nucleotide analogs to synthesize aptamers that are resistant to nucleolytic degradation (16). Targets for aptamer selection typically have been macromolecules with complex surfaces, but several cases of small molecule targets have been reported (17). Although SELEX has the potential to identify high-affinity ligands to a wide variety of...

show abstract

Section: ϫ7mentioning

confidence: 57%

DNA ligands that bind tightly and selectively to cellobiose

Yang

Goldstein

Mei

et al. 1998

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

106

View full text Add to dashboard Cite

show abstract

“…It was pointed out before that the fact that RNA molecules can bind aminoglycosides may indicate that these antibiotics have evolved to exploit speci®c recognition of nucleic acids (Davies et al, 1993;Lato et al, 1995). The occurrence of similar arrangements of Mg 2 at the active sites of both ribozymes and polymerases, forming possible targets for electrostatically complementary binding of aminoglycosides, predestinates the fragments of naturally occurring aminoglycosides as versatile templates for the construction of small molecularmass effectors.…”

Section: Discussionmentioning

confidence: 99%

Aminoglycoside binding to the hammerhead ribozyme: a general model for the interaction of cationic antibiotics with RNA 1 1Edited by J. Karn

Hermann

Westhof

1998

Journal of Molecular Biology

181

166

View full text Add to dashboard Cite

A variety of drugs inhibit biological key processes by binding to a speci®c RNA component. We focus here on the well-analysed hammerhead ribozyme RNA that is inhibited by aminoglycoside antibiotics, a process considered as a paradigm for studying drug/RNA interactions. With insight gained from molecular dynamics simulations of the ribozyme in the presence of Mg 2 identi®ed by crystallography and of aminoglycosides in solution, a general model for aminoglycoside binding to RNA is proposed. A striking structurally based complementarity between the charged ammonium groups of the aminoglycosides and the metal binding sites in the hammerhead was uncovered. Despite dynamical exibility of the aminoglycosides, several of the intramolecular distances between the charged ammonium groups of the drugs were found to be rather constant. Intramolecular ammonium distances of the aminoglycosides span ranges similar to the interionic distances between Mg 2 in the hammerhead. Successful docking of aminoglycosides to the hammerhead ribozyme could be achieved by positioning the ammonium groups at the sites occupied by Mg 2 . The covalently linked ammonium groups of the aminoglycosides are thus able to complement in space the negative electrostatic potential created by a three-dimensional RNA fold. Consequently, it is suggested that aminoglycoside-derived sugars could constitute a basic set of yardstick synthons ideal for rational and combinatorial synthesis of drugs targeted at biologically relevant RNA folds.

show abstract

“…Examples range from natural molecules such as amino acids (1)(2)(3)(4), biological cofactors (5-9), alkaloids (10) and aminoglycoside antibiotics (11)(12)(13) to abiotic organic dyes (14,15) and transition state analogues (16,17). Furthermore, nucleic acid aptamers which bind to and sometimes inhibit the GenBank accession nos U37123 and U37124 activity of a great variety of proteins have been isolated [for reviews see e.g.…”

Section: Introductionmentioning

confidence: 99%