Mimicking organic enzyme

Chemists have long recognized that the easiest way to evaluate this situation is to examine model reactions in organic or mixed aqueous phases. We have described a model system that mimicked an enzyme in such a mixed solvent but not in water (II). Thus, it was... 

Both the G- and V-agents have the same physiological action on humans. They are potent inhibitors of the enzyme acetylcholinesterase (AChE), which is required for the function of many nerves and muscles in nearly every multicellular animal. Normally, AChE prevents the accumulation of acetylcholine after its release in the nervous system. Acetylcholine plays a vital role in stimulating voluntary muscles and nerve endings of the autonomic nervous system and many structures within the CNS. Thus, nerve agents that are cholinesterase inhibitors permit acetylcholine to accumulate at those sites, mimicking the effects of a massive release of acetylcholine. The major effects will be on skeletal muscles, parasympathetic end organs, and the CNS. 

The most promising direction for enzyme modeling is to synthetically mimick the nature of the binding site and the active site in terms of the close similarity of catalytic groups, stereochemistry, interatomic distances and the mechanism of the action of the enzyme. Mimicking of the proton-transfer relay proposed for the mechanism of the action of chymotrypsin is a brilliant example of such work (D Souza and Bender, 1987 and references therein). The miniature organic model of chymotrypsin built on the basis of cyclodextrin and the mechanism of hydrolysis m-tert-butylphenyl acetate is presented in Fig. 6.9. 

A living organism is more than just a collection of enzymes and other important species—it is an organized collection. The components of the ceU are compartmentalized into organelles such as the nucleus, and the cell is strucmred additionally by internal and external membranes. This powerful type of system still waits to be fully mimicked. 

This work on organic reaction mechanisms and our development of cyclophane chemistry were of great use to us in our later work. We did not shy away from tackling either multistep syntheses (up to 30 reactions) or highly asymmetric, designed systems needed in our studies of enzyme-mimicking systems. We needed both equilibria and kinetic techniques and an understanding of the importance of solvent effects in our more recent studies. 

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