Structural Determinants of Conformationally Selective, Prion-binding Aptamers[boxs]

We have recently described the isolation of 2′-fluoropyrimidine-substituted RNA aptamers that bind selectively to disease-associated β-sheet-rich forms of the prion protein, PrP, from a number of mammalian species. These aptamers inhibit the accumulation of protease-resistant forms of PrP in a prion...

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Bibliographic Details
Published in:The Journal of biological chemistry 2004-03, Vol.279 (13), p.13102-13109
Main Authors: Sayer, Natalie M., Cubin, Matthew, Rhie, Alexandre, Bullock, Marc, Tahiri-Alaoui, Abdessamad, James, William
Format: Article
Language:English
Subjects:
Animals
Base Sequence
Binding Sites
Biotinylation
Cattle
Dose-Response Relationship, Drug
Electrophoresis, Polyacrylamide Gel
Escherichia coli - metabolism
Kinetics
Molecular Sequence Data
Prions - chemistry
Protein Binding
Protein Conformation
Protein Folding
Protein Structure, Secondary
RNA - chemistry
Transcription, Genetic
Urea - pharmacology
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Summary:We have recently described the isolation of 2′-fluoropyrimidine-substituted RNA aptamers that bind selectively to disease-associated β-sheet-rich forms of the prion protein, PrP, from a number of mammalian species. These aptamers inhibit the accumulation of protease-resistant forms of PrP in a prion-seeded, in vitro conversion assay. Here we identify the minimal portions of two of these aptamers that retain binding specificity. We determine their secondary structures by a combination of modeling and solution probing. Finally, we identify an internal site for biotinylation of a minimized, synthetic aptamer and use the resultant reagent in the detection of abnormal forms of PrP in vitro.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M310928200