Receptor+assisted+casting

Receptor assisted casting

Receptor assisted casting is a form of thermodynamic templating. In thermodynamic templating, the equilibrating constituents interact with the target or template molecule, and the equilibrium shifts towards the thermodynamically most favourable dynamic library member. This, in turn, causes an amplification of the thermodynamically most favourable member, which can be removed from the mixture by halting the dynamic reaction equilibrium by a variety of possible methods, including alteration of various environmental aspects, such as pH of the solution [1]. Additionally, the favoured member can be assessed //in situ// by a variety of methods, including NMR, which ensures that the change in the chemical environment required to halt the equilibrium does not impact the energetics of the system and, consequently, the amplified member.

Figure 1 : Receptor assisted casting in dynamic combinatorial libraries. The building blocks are present on the left, the various library members that are formed from these building blocks are represented in the middle and the right side of the figure indicates the amplified library member (bigger brown molecule) along with the receptor that led to the amplification. The hooks represents the reversible bonds between the building blocks. With the help of receptor assisted casting method, the structure of the receptor site of a biological molecule, such as an enzyme, can be determined [3]. This can be done via interpretation of the structure and properties of the amplified member after the dynamic reaction has been halted and the amplified member has been extracted [3]. Through this methodology, highly effective inhibitors of various enzymes, including carbonic anhydrase, have been identified [3 ].

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