The Basis for Allosteric Effectors as Potential Therapeutic Agents

Types of considerations suggesting how "allosteric" drugs of various types might be designed are schematically illustrated in Figs.

9.15 and 9.16. For heterotropic effects a drug might bind but not trigger the necessary allosteric change. For either homotropic or heterotropic effects a drug might be designed thal stabilizes the region of the molecule across which the allosteric change must be transmit. ted, thus blocking the required allosteric transition. Finally, if an MWC type model is ir effect, yet a third type of "allosteric" drug car be envisaged, one that stabilizes either the E or T state as appropriate without directly impacting either the normal allosteric regulatoi binding or the regions of the molecule involvec in the normal conformational change. Such £ drug would bind to some aspect of the confer-

Type 2 Allosteric drug binds to newly designed allosteric site and produces desired effect

Newly designed allosteric site on protein

Type 2 Allosteric drug binds to newly designed allosteric site and produces desired effect

Natural allosteric regulator site

Type 1 Allosteric drug binds to normal allosteric site and produces desired effect mation of either the R or T state distinct for that state and displace the equilibrium between R and T toward the appropriate state, as shown in Fig. 9.16.

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