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Published Online March 10, 2005
Science DOI: 10.1126/science.1109999

Reports

Submitted on January 21, 2005
Accepted on March 1, 2005

Amplification of Acetylcholine-Binding Catenanes from Dynamic Combinatorial Libraries

Ruby T. S. Lam 1, Ana Belenguer 1, Sarah L. Roberts 1, Christoph Naumann 1, Thibaut Jarrosson 1, Sijbren Otto 1, Jeremy K. M. Sanders 1*

1 Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.

* To whom correspondence should be addressed.
Jeremy K. M. Sanders , E-mail: jkms{at}cam.ac.uk

Directed chemical synthesis can produce a vast range of molecular structures, but the intended product must be known at the outset. In contrast, evolution in nature can lead to efficient receptors and catalysts whose structures defy prediction. To access such unpredictable structures, we have prepared dynamic combinatorial libraries, in which reversibly-binding building blocks assemble around a receptor target. We selected for an acetylcholine receptor by adding the neurotransmitter to chloroform/dimethylsulfoxide solutions of dipeptide hydrazones [proline-phenylalanine or proline-(cyclohexyl)alanine], which reversibly combine through hydrazone linkages. At thermodynamic equilibrium, the dominant receptor structure was an elaborate [2]-catenane, consisting of two interlocked macrocyclic trimers. This complex receptor with a 100 nanomolar affinity for acetylcholine could be isolated on a preparative scale in 65% yield.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Molecular Recognition and Self-Assembly Special Feature: Dynamic combinatorial synthesis of a catenane based on donor-acceptor interactions in water.
H. Y. Au-Yeung, G. D. Pantos, and J. K. M. Sanders (2009)
PNAS 106, 10466-10470
   Abstract »    Full Text »    PDF »
Dynamic donor acceptor [2]catenanes.
O. S Miljanic and J. F. Stoddart (2007)
PNAS 104, 12966-12970
   Abstract »    Full Text »    PDF »


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Science. ISSN 0036-8075 (print), 1095-9203 (online)