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Amplification of acetylcholine-binding catenanes from dynamic combinatorial libraries
Ruby T S Lam1, Ana Belenguer, Sarah L Roberts
1Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.
Science (New York, N.Y.)
|March 12, 2005
Summary
Researchers created dynamic combinatorial libraries to discover unpredictable molecular structures. They identified a novel catenane receptor for acetylcholine with high affinity and yield.
Area of Science:
- Chemical synthesis
- Molecular biology
- Supramolecular chemistry
Background:
- Directed synthesis requires predefined targets, limiting access to novel structures.
- Nature's evolutionary processes yield unpredictable, efficient receptors and catalysts.
Purpose of the Study:
- To develop a method for accessing unpredictable molecular structures using dynamic combinatorial libraries.
- To identify novel receptors by selecting for specific molecular targets.
Main Methods:
- Preparation of dynamic combinatorial libraries using reversibly binding dipeptide hydrazones.
- Selection of acetylcholine receptors by introducing the neurotransmitter.
- Analysis of receptor structures at thermodynamic equilibrium.
Main Results:
- The dominant assembled structure was an elaborate [2]-catenane, composed of two interlocked macrocyclic trimers.
- The catenane receptor exhibited a high affinity of 100 nM for acetylcholine.
- The receptor was successfully isolated on a preparative scale with a 67% yield.
Conclusions:
- Dynamic combinatorial libraries enable the discovery of complex, unpredictable molecular architectures.
- This approach provides a powerful strategy for designing synthetic receptors with high specificity and affinity.
- The identified catenane represents a novel class of receptors with potential applications in molecular recognition and drug design.