Enzyme mimic catalysis

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]. 

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. 

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. 

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. 

CDs are cyclic oligosaccharides comprised of a-l,4-linked glucopyr-anose units (37- 0). The following properties make CDs attractive components in organic chemistry and supramolecular catalysis/ enzyme mimics in particular (i) CDs are water soluble (ii) their hydrophobic cavity can host a variety of lipophilic guest molecules ... 

Tada, M. and Iwasawa, Y. (2009) Model Systems in Catalysis From Single Crystals and Size Selected Clusters to Supported Enzyme Mimics (ed. R.M. Rioux), Springer, in press. 

Similarly to their natural counterparts (enzymes, antibodies, and hormone receptors), MIPs have found numerous applications in various areas. They have been used as antibody mimics in immunoassays and sensors and biochips as affinity separation materials and for chemical and bioanalysis, for directed synthesis and enzyme-like catalysis, and for biomedical applications. Concerning their commercialization, there has been great progress during the past decade, in particular in the... 

Catalytic antibodies, predicted by Jencks in 1969 and first discovered in 1986, can now be raised against a wide variety of haptens covering nearly every reaction. Catalytic antibodies are regarded as the best enzyme mimics, with very good selectivity, but almost always their catalytic efficiency is by far insufficient. Some natural RNA molecules act as catalysts with intrinsic enzyme-like activity which permits them to catalyze chemical reactions in the complete absence of protein cofactors. In addition, ribozymes identified through in-vitro selection have extended the repertoire of RNA catalysis. This versatility has lent credence to the idea that RNA molecules may have been central to the early stages of life on Earth. 

However, the results obtained in recent years have also established that the structural characteristics of the established dendrimer systems, such as the absence of a well-defined secondary structure, have limited the development of efficient abiotic enzyme mimics based on dendrimers. To achieve this ambitious goal, more efforts in dendrimer synthesis will be necessary. The use of dendritic catalysts in biphasic solvent systems has only just begun and appears to be a particularly fruitful field for further developments. These utilitarian aspects aside, it is the aesthetic attraction of these topologically highly regular macromolecules that continues to fascinate those working in the field of dendrimer catalysis. 

Artificial enzymes with metal ions can also hydrolyze phosphate esters (alkaline phosphatase is such a natural zinc enzyme). We examined the hydrolysis of p-nitro-phenyfdiphenylphosphate (29) by zinc complex 30, and also saw that in a micelle the related complex 31 was an even more effective catalyst [118]. Again the most likely mechanism is the bifunctional Zn-OH acting as both a Lewis acid and a hydroxide nucleophile, as in many zinc enzymes. By attaching the zinc complex 30 to one or two cyclodextrins, we saw even better catalysis with these full enzyme mimics [119]. A catalyst based on 25 - in which a bound La3+ cooperates with H202, not water - accelerates the cleavage of bis-p-nitrophenyl phosphate by over 108-fold relative to uncatalyzed hydrolysis [120]. This is an enormous acceleration. 

R.M. Rioux (ed.). Model Systems in Catalysis Single Crystals to Supported Enzyme Mimics, DOl 10.1007/978-0-387-98049-2 l, Springer Science+Business Media, LLC 2010... 

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