Transformations SELECT Duplication

SELECT Duplication, SELECT-to-SELECT Transfer, and SELECT Output Closure are often used together with the Process Creation and Pipestage Creation transformations described later to form pipestages. 

Dimerization of a biologically active molecule represents an alternative approach in the optimization process of a lead compound. Generally, the duplication of the pharmacophore leads to an equivalent or more active derivative which exhibits different selectivity profile and pharmacokinetic properties. Enzyme inhibition will be improved when using homodimer inhibitors. Antagonists and agonists of specific receptors could be transformed respectively into agonists and antagonists of another receptor subtype. Several examples will be reported and discussed below. 

The SELECT transformations allow the designer to interactively manipulate SELECTS and the operators surrounding them. Operators can be moved into and out of SELECTS, nested SELECTS can be combined, and SELECTS can be duplicated. 

The SELECT-to-SELECT Transfer transformation is applied interactively to move an operator from a branch in one SELECT to the end of the corresponding branch in the immediately preceding duplicate SELECT. An example of SELECT-to-SELECT Transfer is shown in Figure 3-11, where the shaded operator is moved to the corresponding branch in the previous SELECT if each SELECT will later become a separate pipestage, this moves the shaded operator into an earlier stage. 

The biochemistry catalyzed by enzymes that use coenzyme B12 is particularly interesting. As an example, methylmalonyl CoA (15) can reversibly rearrange to succinyl CoA (16). Many other reactions are of this type, in which a hydrogen atom and another group change places along an ethano system. There is as yet no chemical process by which one can duplicate such reactions, regardless of rate. Thus in this case an enzyme mimic is needed not just to come up to the rate and selectivity of an enzyme, but indeed even to perform the chemical transformation itself. 

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