Structural Determinants of Conformationally Selective, Prion-binding Aptamers

Structural Determinants of Conformationally Selective, Prion-binding Aptamers
March 26, 2004
Natalie M. Sayer, Matthew Cubin, Alexandre Rhie, Marc Bullock, Abdessamad Tahiri-Alaoui, and William James
J. Biol. Chem.
We have recently described the isolation of 2'-fluoropyrimidine-substituted RNA aptamers that bind selectively to disease-associated -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.
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