Enzyme-Analogous Catalysts

The capabilities of enzymes to transform organic substrates smoothly, in good yields, and highly selectively, have stimulated the desire of organic chemists to tailor catalysts with similar features for specific reactions. 

In this respect, reactions catalyzed by monoclonal antibodies have been the focus of much interest [72]. One of the first antibody-supported syntheses on a gram scale and with an enantiomeric excess of up to 99 % was the kinetic resolution of aldol adducts. The products resulting from the retro-aldol reaction served as precursors in the synthesis of epothilones A and B [73]. 

For the production of an effective monoclonal antibody it is crucial to raise it from a well-designed transition state analogue. Besides not resembling the product too much in order to avoid product inhibition, this hapten should mimic the transition state as closely as possible to maximize its stabilization by the antibody generated. Utilizing the extraordinary specificity of the immune system by this means, the combining site of the antibody is programmed to exhibit a specific catalytic activity. This technique has been directed toward the development of selective reactions which are chemically difficult to achieve, for example disfavored , and for which no suitable enzyme is available. 

Ribonucleic acids (RNAs) were employed as catalysts in the synthesis of amides and esters, peptide bond formation and Diels-Alder reactions. The approach suffers from the fact that it requires the reactants to be either RNA itself or a compound covalently tethered to RNA. Indeed, there is one prominent example where RNA acts as a true catalyst in a bimolecular Diels-Alder cycloaddition without tethering the substrates [11.  

The chemical modeling of active sites of enzymes can help to gain deeper insight into their catalytic mechanisms and might also lead to enzyme substitutes which are reliable and easy-to-handle tools for organic synthesis. Recently, it 

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Polymeric enzymes and enzyme analogs constitute a completely separate topic. This field has recently been reviewed 133). Some of the materials described act as heterogeneous catalysts and could also be considered as polymeric heterogeneous catalysts. 

How remarkable is life The answer is very. Those of us who deal in networks of chemical reactions know of nothing like it. We understand some - but only some -of the characteristics of the network that make it so remarkable. One key to its behavior is catalysis. The rates of essentially all cellular reactions - the processes that convert one molecule into another - are controlled by other molecules (usually by a class of protein catalysts called enzymes). The catalysts are (in some sense) like valves in a chemical plant (which, in some sense, is what a cell is) they control the rate at which one kind of molecule becomes another in a way loosely analogous to that in which a valve controls the rate at which fluid flows through a pipe. The complexity of the network becomes clear when one realizes that the catalysts - the valves - are themselves controlled by the molecules they produce the products of one reaction can control the rate at which another reaction takes place. 

The chemical interest of these trace amount proteins stems from the fact that they can be used as catalysts or enzyme analogs for almost any chemical reaction (Tramontano et al., 1986 Pollack et al., 1986 Lemer et al., 1991). The fundamental difference between antibodies and enzymes does not relate so much to the protein structures as to the structure and lifetime of the substrates. Antibodies selectively bind molecules in their ground state, whereas enzymes selectively produce and then bind more strongly to short-lived transition states. Antibody-antigen complexes tend toward precipitation, whereas enzyme-transition state complexes react to enzyme-product complexes, which immediately dissociate. In both cases, however, the same noncovalent bonds are used. 

Schultz C, Groeger H, Dinkel C, Drauz K, Waldmann H (2002) Special catalysts and processes biocatalysis and enzyme-analogous processes. In CornUs B, Herrmann WA (eds) Applied homogeneous catalysis with organometaUic compounds, 2nd edn. WUey-VCH,Weinheim,p 872... 

The cyclic phosphonate ester analog of the cyclic transition state. Antibodies raised against this phosphonate ester act as enzymes they are catalysts that markedly accelerate the rate of ester hydrolysis. 

Several approaches to enantioselective synthesis have been taken, but the most efficient are those that use chiral catalysts to temporarily hold a substrate molecule in an unsymmetrical environment—exactly the same strategy that nature uses when catalyzing reactions with chiral enzymes. While in that unsymmetrical environment, the substrate may be more open to reaction on one side than on another, leading to an excess of one enantiomeric product over another. As an analog)7, think about picking up a coffee mug in your... 

Microbes tend to form flocks as they grow, into which nutrients and dissolved oxygen must diffuse. The rate of growth thus depends on the diffusional effectiveness. This topic is developed by Atkinson (1974). Similarly enzymes immobilized in gel beads, for instance, have a reduced catalytic effectiveness analogous to that of porous granular catalysts that are studied in Chapter 7. For the M-M equation this topic is touched on in problems P8.04.15 and P8.04.16. 

In the present paper we are concerned principally with the initiation step. The new observations and suggestions regarding this step put forward by Polanyi and his collaborators [17-21] marked the first real practical and theoretical advance since the work of Whitmore. They found that in the polymerization of isobutene by TiCl4 or BF3, both at room temperature and at very low temperatures, the metal halide alone was inactive, and that a third component, the co-catalyst, was required to initiate the polymerization. The word co-catalyst was chosen for the substances concerned, by analogy with co-enzyme . It is to be preferred to the term promoter , often used by American workers, as this indicates a substance which speeds up a reaction which would also take place in its absence, and since the characteristic of co-catalysts is that they are essential to the reaction. The first co-catalyst to be discovered was water, but shortly afterwards certain alcohols and acids were found to act in a similar manner. 

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