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REMOTE CONFORMATIONAL CONTROL

Obiettivo

Stereochemistry can be viewed as binary information, and stereocontrol as the communication of that information through space. Reliable stereochemical control is mediated by conformation, and empirically it is clear that better control of conformation yields higher stereoselectivity.

In this project we propose to develop the methods of stereocontrol and apply them more generally to the problem of communicating information through space, mediated not by electronics but by conformation. We shall identify molecular fragments whose conformation is readily controlled by local stereochemistry, and which are able to propagate conformation through a molecule by a series of relayed interactions. Conformational communication is not a concept familiar in chemistry, but is central to the phenomenon of allostery in biology. In an allosteric protein, haemoglobin being the classic example, the binding of a ligand leads to a conformational change which propagates through the molecule, leading to a remote alteration of stereochemistry (conformation) and hence modulating the binding affinity of further ligands.

Conformational changes in transmembrane proteins likewise communicate information between binding sites on opposite sides of the membrane. As chemists, we aim to design conformationally linked receptors and effectors and demonstrate the potential for chemical allostery in information transfer and processing. The molecules we propose to study are oligoureas, known to adopt a helical conformation, and we shall combine structural studies of these molecules with the methods of stereoselective synthesis in order to construct molecules capable of relaying, and ultimately processing, stereochemical information.

Invito a presentare proposte

FP6-2002-MOBILITY-5
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Coordinatore

VICTORIA UNIVERSITY OF MANCHESTER
Contributo UE
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Indirizzo
OXFORD ROAD
10142 MANCHESTER
Regno Unito

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Collegamenti
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