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Nucleic Acids Research 2005 33(17):5602-5610; doi:10.1093/nar/gki867
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Published online 30 September 2005

© The Author 2005. Published by Oxford University Press. All rights reserved
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions{at}oxfordjournals.org

Article

In vitro selection of RNA aptamers against a composite small molecule-protein surface

Kelly A. Plummer1, James M. Carothers3, Masahiro Yoshimura1, Jack W. Szostak3 and Gregory L. Verdine1,2,*

1Department of Chemistry and Chemical Biology, Harvard University Cambridge, Massachusetts 02138, USA 2Department of Molecular and Cellular Biology, Harvard University Cambridge, Massachusetts 02138, USA 3Howard Hughes Medical Institute and Department of Molecular Biology, Massachusetts General Hospital Boston, Massachusetts 02114, USA

*To whom correspondence should be addressed. Tel: 617 495 5323; Fax: 617 495 8755; Email: verdine{at}chemistry.harvard.edu

Received July 20, 2005. Revised September 9, 2005. Accepted September 9, 2005.

A particularly challenging problem in chemical biology entails developing systems for modulating the activity of RNA using small molecules. One promising new approach towards this problem exploits the phenomenon of ‘surface borrowing,’ in which the small molecule is presented to the RNA in complex with a protein, thereby expanding the overall surface area available for interaction with RNA. To extend the utility of surface borrowing to include potential applications in synthetic biology, we set out to create an ‘orthogonal’ RNA-targeting system, one in which all components are foreign to the cell. Here we report the identification of small RNA modules selected in vitro to bind a surface-engineered protein, but only when the two macromolecules are bound to a synthetic bifunctional small molecule.

Present address: Masahiro Yoshimura, Research Center for Materials Science and Department of Chemistry, Nagoya University, Chikusa, Nagoya 464-8602, Japan


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