Enzyme mimics, design

Scheme 1 is a gross over-simplification for almost any enzyme-catalyzed reaction of a specific substrate, based as it is on a one-step reaction with a single, rate-determining transition state but it is appropriate for many, if not most reactions catalyzed by simple enzyme mimics. Most important for present purposes, it emphasises the most important properties of enzyme reactions which the design of mimics, or artificial enzymes, must address, namely ... 

Design and Synthesis of Enzyme Mimics of P-Carotene 15,15 -monooxygenase 35... 

There are two approaches to the discovery of enzyme mimics, i.e., to identify molecules that are able to bind substrate (s) and then catalyze reactions (Rowan, 1997). The first approach, often inspired by enzymes themselves, utilizes chemical knowledge and experience to design the catalyst The other approach is to create a library and select the best host for a transition-state analog of the required reaction. The second approach, i.e., the combinatorial search, is covered in Chapter 11 the first one is discussed below. This first approach, the finding of enzyme mimics, has been reviewed by Kirby (1996) and Reichwein (1994), among others. 

The production of various half-finished products of petrochemical synthesis and liquid fuels from natural gas is the most important objective connected with the crude oil economy and the creation of highly effective chemical engineering processes. In this connection, investigations performed by the Sandra National Laboratory (USA) are of special interest. This company designs enzyme mimics for catalytic activation of low-molecular gaseous alkanes in liquid fuel production [74], Two directions of their activity should be outlined ... 

In conclusion, the aldol reaction with L-proline as an enzyme mimic is a successful example for the concept of using simple organic molecules as chiral catalysts. However, this concept is not limited to selected enzymatic reactions, but opens up a general perspective for the asymmetric design of a multitude of catalytic reactions in the presence of organocatalysts [1, 3]. This has been also demonstrated by very recent publications in the field of asymmetric syntheses with amino acids and peptides as catalysts. In the following paragraphs this will be exemplified by selected excellent contributions. 

Significant improvements in the properties can also be achieved by using the various types of functionalized surfactant aggregates. Scientific endeavors for the design of enzyme mimics will continue until natural enzymes are engineered such that they can participate in the processes such as decontamination of toxic substances. 

Cyclodextrins have proven to be the most popular enzyme mimics, catalyzing various reactions. Cyclodextrin-based neoglycoenzymes with improved efficiency have also been designed and synthesized. Cyclodextrin-modified enzymes have potential application as biosensors as well as in the formulation of effective and biodegradable drug delivery systems for enzyme replacement therapy [84]. 

Design of catalysts mimicking the catalytic principles of enzymes is among the great challenges of modern chemistry (9, 10). Catalytic antibodies are examples of semisynthetic artificial enzymes (11-14). Fully synthetic molecules also have been designed as enzyme mimics by using either peptidic (15, 16) or nonpeptidic (17-24) molecules. 

A different approach has been reported by Benner and his group, [26] who based the design of a synthetic decarboxylase on the known properties of proteins and the mechanism of amine-catalysed decarboxylation of 0-ketoacids. Their enzyme mimics are 14-... 

Tlie basic study of intermolecular interactions is facihtated by one-bead-one-stRicture libraries which can be powerful tools for the discovery of hgands to synthetic receptors and vice versa. Encoded combinatorial libraries have been useful for disclosing ligands for well-designed macrocyclic host molecules and to elucidate their specificities for peptide sequences. These studies led via receptors with more flexibility to simple host molecules without elaborate design that ai e accessible to combinatorial synthesis. One application is the development of chemical sensors for analytes that are otherwise difficult to detect or only non-specificaUy detected. Such hbraries have been used to find new catalysts and enzyme mimics. 

The imidazolyl group, a constituent of histidine, provides some crucial catalytic sites for enzymatic catalysis. The investigations on enzyme mimics constitute a major contemporary research area in supramolecular chemistry. The synthetic designs of enzyme mimics should necessarily possess a hydrophobic cavity and suitably preorganized functional... 

Another often applied approach to enzyme mimics is imprinting a polymer containing catalytically active groups with a substrate analogue. For example, a polymer containing Co(II)-imidazole complexes imitating the active site of the phosphotriesterase enzyme was designed... 

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