Mimics, enzyme

Azacrown ethers as enzyme mimics of ATPase 99MI17. 

Walter C. J., Mackay L. G., Sanders JKM Can Enzyme Mimics Compete With Catalytic Antibodies NATO ASISer., Ser. E1996 320 419-428... 

Keywords Diels-Alder reaction enzyme mimic... 

Sanders JKM Enzyme Mimics Proc. - Indian Acad. Sci., Chem. Sci. 1994 106 983-988... 

Keywords enzyme mimics for catalysis of Diels-Alder reaction... 

The field of synthetic enzyme models encompasses attempts to prepare enzymelike functional macromolecules by chemical synthesis [30]. One particularly relevant approach to such enzyme mimics concerns dendrimers, which are treelike synthetic macromolecules with a globular shape similar to a folded protein, and useful in a range of applications including catalysis [31]. Peptide dendrimers, which, like proteins, are composed of amino acids, are particularly well suited as mimics for proteins and enzymes [32]. These dendrimers can be prepared using combinatorial chemistry methods on solid support [33], similar to those used in the context of catalyst and ligand discovery programs in chemistry [34]. Peptide dendrimers used multivalency effects at the dendrimer surface to trigger cooperativity between amino acids, as has been observed in various esterase enzyme models [35]. 

French, R. R. et al. (2000). A supramolecular enzyme mimic that catalyzes the 15,15 double bond scission of beta,beta-carotene. Angew. Chem. Int. Ed. 39(7) 1267-1269. 

There is another approach that is increasingly part of synthesis the use of enzymes as catalysts. This approach is strengthened by the new ability of chemists and molecular biologists to modify enzymes and change their properties. There is also interest in the use of artificial enzymes for this purpose, either those that are enzyme-like but are not proteins, or those that are proteins but based on antibodies. Catalytic antibodies and nonprotein enzyme mimics have shown some of the attractive features of enzymes in processes for which natural enzymes are not suitable. 

Abstract This chapter updates but mostly supplements the author s Ange-wandte Review,111 setting in context recent advances based on protein and nucleic acid engineering. Systems qualify as a true enzyme mimics if there is experimental evidence for both the initial binding interaction and catalysis with turnover, generally in the shape of saturation kinetics. They are discussed under five broad headings mimics based on natural enzymes, on other proteins, on other biopolymers, on synthetic macromolecules and on small-molecule host-guest interactions. 

This chapter will consider some of the most interesting of current approaches to the evolution of enzyme mimics, in the context of continuing dramatic progress in protein and nucleotide engineering. There are excellent practical as well as intellectual reasons for the broad interest in this topic. Catalysis is a major preoccupation of the chemical industry if the application of the principles of biocatalysis can lead to robust and efficient catalysts tailor-made for reactions of economic importance the area will become even more a focus of intense activity and investment. 

Enzyme mimics catalyze reactions by mechanisms which are demonstrably enzyme-like. The minimum requirement is that the reactions concerned should involve an initial binding interaction between the substrate and the catalyst. This gives rise to Michaelis-Menten kinetics reactivity is measured in terms of the familiar parameters kCat and Km and we use E to denote enzyme mimic as well as enzyme. ... 

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 ... 

Mimics based on natural enzymes Mimics based on other proteins Mimics based on other biopolymers Mimics based on synthetic macromolecules Mimics based on small-molecule host-guest interactions... 

Cyproase 1 is in effect a new enzyme, produced by systematic protein engineering firmly based on sound chemical principles. Its status as an enzyme mimic may be debatable its efficiency is not. It was shown to hydrolyze 25% of bonds to proline in a (denatured) peptide toxin in two hours at pH 70, with some 400 turnovers. It is one of the two most efficient enzyme mimics we will encounter in this article1131... 

The Kemp elimination is of special interest because it is known to be extraordinarily sensitive to the medium, and particularly well suited as a test reaction for potential enzyme mimics because it is a simple, one-step process. The joint conclusions from this work were that catalysis involves a combination of a number of different factors, even for this simple reaction by these simple catalysts. 

DNA binds and reacts with carcinogenic and similar compounds which alkylate it through cationic intermediates, in some cases extraordinarily fast 1371 and can in the process catalyse the hydrolysis of some substrates, like the bay-region diol epoxides derived from benzpyrene.1381 In the context of enzyme mimics these reactions are primarily of curiosity value DNA lacks the conformational flexibility and the chemical functionality to offer the prospect of efficient catalysis for ordinary reactions. 

Finally, the most complex synthetic reaction clearly catalysed by RNA molecules generated by in vitro selection is the formation of the C-N bond of a nucleoside (Scheme 7), from 4-thiouracil and most of the natural substrate for the natural (uracil phos-phoribotransferase) reaction.1461. (Thiouracil was used because it is easily tagged by alkylation on sulfur.) The catalytic RNAs produced by 11 rounds of selection required Mg++ cations and had kcat as high as 0.13 min-1,with kcaJKM at least 107 times greater than the (undetectable) uncatalyzed reaction. Once again these systems are convincing, rather efficient enzyme mimics. 

Hence the dimension ("the order") of the reaction is different, even in the simplest case, and hence a comparison of the two rate constants has little meaning. Comparisons of rates are meaningful only if the catalysts follow the same mechanism and if the product formation can be expressed by the same rate equation. In this instance we can talk about rate enhancements of catalysts relative to another. If an uncatalysed reaction and a catalysed one occur simultaneously in a system we may determine what part of the product is made via the catalytic route and what part isn t. In enzyme catalysis and enzyme mimics one often compares the k, of the uncatalysed reaction with k2 of the catalysed reaction if the mechanisms of the two reactions are the same this may be a useful comparison. A practical yardstick of catalyst performance in industry is the space-time-yield mentioned above, that is to say the yield of kg of product per reactor volume per unit of time (e.g. kg product/m3.h), assuming that other factors such as catalyst costs, including recycling, and work-up costs remain the same. 

N. Herron, Toward Si-based hfe Zeolites and enzyme mimics, Chemtech 19, 542-548 (1989). 

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

Fig. 9. Cleavage of the substrate analogue 27 by the enzyme mimic 24+TBHP.

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