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Dalton Trans. 2006 Jun 21;(23):2861-4. Epub 2006 May 8.

Reinforced molecular recognition as an alternative to rigid receptors.

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  • 1Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, UKCB2 1EW.


In theory, a perfectly rigid receptor will probably be an unbeatable binder. However, rigidity may not be easy to achieve in practice and it is certainly not Nature's method to realise high affinity. In many proteins binding affinity is increased through non-covalent interactions within the protein. Thus there is a considerable incentive to follow Nature's example and start exploring the use of secondary intra-receptor interactions to aid in the binding process. Secondary interactions within a receptor will reinforce host-guest binding when the same conformational rearrangement (or freezing of motion) is required for guest binding as for the formation of the intra-receptor interactions. Introducing secondary interactions will require rather elaborate synthetic receptors to be produced. With the recent developments in dynamic combinatorial chemistry, access to the desired structures should be facilitated. Whether or not this approach will develop into a practical method remains to be established, but even if it does not, efforts along these lines will lead to a better understanding of the complex interplay between molecular recognition, folding and dynamics.

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