Artificial enzyme systems

One of the great intellectual challenges presented to Science by Nature is a proper understanding of how enzymes work. At one level we can, explain enzyme catalysis - what an enzyme does is bind, and thus stabilise, selectively the transition state for a particular reaction. [7] But our current level of understanding fails the more severe, practical test - that of designing and making artificial enzyme systems with catalytic efficiencies which rival those of natural enzymes. 

Leznoff has published further on the solid-phase synthesis of insect sex attrac-tants. The advantages and uses of enzymes attached to solid supports have been reviewed. Aspects of triphase catalysis (organic layer-water-polymer) have been discussed by Regen, while advances in phase-transfer catalysis have been reviewed. A crown ether NAD(P)H mimic has been described,bringing synthetic chemists nearer to the objective of artificial enzyme systems. 

One of the greatest obstacles in the successful modeling of the cytochrome P-450 system is the choice and control of electrons for the reductive activation of dioxygen. In our laboratory we began by designing a system that closely matched the environment of the native enzyme. Artificial bilayers in the form of polymerizied vesicles of 9 were utilized in an attempt to compartmentalize and separate the various components of the artificial enzyme system (Figure 7).2i... 

So why should anyone want to build mimics which are bound to be inferior to the real thing Precisely because we want to discover the rules that we don t know As Kirby points out,[l] our current level of understanding fails.the severe practical test...of designing and making artificial enzymes systems with catalytic efficiencies which rival those of natural enzymes. Two quite different strategies for developing enzyme mimics are emerging ... 

Immobilized enzyme systems, or more generally structured enzyme systems, can also be used as models for studying complex dynamics in particular, it is possible to elaborate simple artificial enzyme systems able of generating chaotic behaviors, wheras chemical systems exhibiting analog behaviors are much more complex in particular, the number of chemical species involved is more important. ... 

New natural polymers based on synthesis from renewable resources, improved recyclability based on retrosynthesis to reusable precursors, and molecular suicide switches to initiate biodegradation on demand are the exciting areas in polymer science. In the area of biomolecular materials, new materials for implants with improved durability and biocompatibility, light-harvesting materials based on biomimicry of photosynthetic systems, and biosensors for analysis and artificial enzymes for bioremediation will present the breakthrough opportunities. Finally, in the field of electronics and photonics, the new challenges are molecular switches, transistors, and other electronic components molecular photoad-dressable memory devices and ferroelectrics and ferromagnets based on nonmetals. 

When comparing different computational approaches to enzyme systems, several different factors have to be considered, e.g., differences in high-level (QM) method, QM/MM implementation, optimization method, model selection etc. This makes it very difficult to compare different QM/MM calculations on the same system. Even comparisons with an active-site model are not straightforward. It can be argued that adding a larger part of the system into calculaton always should make the calculation more accurate. At the same time, introducing more variables to the calculation also increases the risk of artificial effects. 

As we saw in the previous sections, inclusion compounds have many structural properties which relate them to other systems based on the hierarchy of non-bound interactions, like enzymes or enzyme-substrate complexes. As a matter of fact, most of the so-called artificial enzymes are based on well-known host molecules (e.g. P-cyclodextrin) and are designed to act partly on such bases 108>109). Most of these models, however, take advantage of the inclusion (intra-host encapsulation) phenomena. Construction of proper covalently bound model molecules is a formidable task for the synthetic chemistuo>. Therefore, any kind of advance towards such a goal is welcomed. 

Kudlich M, Keck A, Klein J, Stolz A (1997) Localization of the enzyme system involved in anaerobic reduction of azo dyes by Sphingomonas sp. strain BN6 and effect of artificial redox mediators on the rate of azo dye reduction. Appl Env Microbiol 63 3691-3694... 

For the first time, the use of artificial enzyme membranes allows the study of the interaction between enzyme activity and membrane potential in a well-defined context. Before the recent progress in manufacturing artificial membrane bearing immobilized enzyme, Blumenthal et al.21 described a system in which a papain solution was sandwiched between two cation and anion exchange membranes. Under short-circuit conditions the system was able to generate a current. A nonequiLbrium thermodynamic analysis was developed by the authors. 

The wide variety of enzymes available gives for promise enzymatic derivatization to become a potent analytical tool in the future. Better understanding and theoretical formulations will lead to commercial availability of immobilized enzymes and consequently to more ready use of them. Since in such systems a low content of organic cosolvent in the mobile phase can only be tolerated (whereas a compromise has to be made as far as the optimum mobile phase pH is concerned), artificial enzymes, which are synthetic polymer chains having functional groups that mimic the biocatalytic activity of natural enzymes, are currently being synthesized and investigated as a means to overcome such limitations (276). 

Virtually all biochemical investigations must be carried out in buffered aqueous solutions. The natural environment of biomolecules and cellular organelles is under strict pH control. When these components are extracted from cells, they are most stable if maintained in their normal pH range, usually 6 to 8. An artificial buffer system is found to be the best substitute for the natural cell milieu. It should also be recognized that many biochemical processes (especially some enzyme processes) produce or consume hydrogen ions. The buffer system neutralizes these solutions and maintains a constant chemical environment. 

The preparation and characterization of short peptidic molecules that adopt a stable and predictible structure in solution is a prerequisite for the construction of de now-designed artificial enzymes and proteins. In natural polypeptides, the secondary structures are parts of a larger system and their conformational stability is due to several intra- and interchain non-covalent interactions such as van der Waals forces, electrostatic forces, hydrogen bonding, and hydrophobic forces [2], However, these interactions are less important in short... 

The food industry is a fertile area for biocatalysis applications high-fructose corn syrup (HFCS) from glucose with glucose isomerase, the thermolysin-catalyzed synthesis of the artificial sweetener Aspartame , hydrolysis of lactose for lactose-intolerant consumers, and the synthesis of the nutraceutical i-camitine in a two-enzyme system from "ybutyrobetaine all serve as examples. 

In the catalytic cycle of CYP, reducing equivalents are transferred from NADPH to CYP by a flavoprotein enzyme known as NADPH-cytochrome P450 reductase. The evidence that this enzyme is involved in CYP monooxygenations was originally derived from the observation that cytochrome c, which can function as an artificial electron acceptor for the enzyme, is an inhibitor of such oxidations. This reductase is an essential component in CYP-catalyzed enzyme systems reconstituted from purified components. Moreover antibodies prepared from purified reductase are inhibitors of microsomal... 

Abstract Calix[n]arenes represent a well-known family of macrocyclic molecules with a broad range of potential applications in many branches of supramolecular chemistry. Because of their preorganisation, calix[n] arenes are frequently used as building blocks and molecular scaffolds in the construction of more elaborate systems, such as artificial enzyme biomimetics and receptors. This review is focused on the recent development of calixarene-based anion receptors. 

---