Esterase catalyst

Enzymes Acetylcholin- esterase Catalysts of biochemical reactions (see Section 10.6.)... 

When esterase models are designed, several important and fundamental problems have to be solved. Systematic studies on other interactions, such as hydrogen-bonding and charge-transfer type forces have not been fully performed. Furthermore, various cooperative actions between different kinds of interactions, e. g. the correlation between the attraction of substrate and repulsion of a product by a polyelectrolyte catalyst, has not yet been carried. 

A different task was pursued by the CM of CsA with various maleates 339 [ 148]. The CM demanded in this case the highly active Hoveyda catalyst D, that exhibits potency not reached by the phosphine-containing catalysts C and E. Under the conditions given in Scheme 65, metathesis with maleates 339 led (E)-selectively to the a,/J-unsaturated ester derivatives 340 in high yield. Compounds 340 still demonstrated activity comparable to that of CsA and are thus potential soft drugs via esterase-mediated biotransformation to the corresponding inactive carboxylic acids 341. 

Estane VC products, 201 Ester-amide copolymers, 146, 147 Esterases, 82 Esterification, direct, 63 Ester interchange catalysts, 71 Ester interchange reactions, 31, 62-63,... 

Esterases have a catalytic function and mechanism similar to those of lipases, but some structural aspects and the nature of substrates differ [4]. One can expect that the lessons learned from the directed evolution of lipases also apply to esterases. However, few efforts have been made in the directed evolution of enantioselective esterases, although previous work by Arnold had shown that the activity of esterases as catalysts in the hydrolysis of achiral esters can be enhanced [49]. An example regarding enantioselectivity involves the hydrolytic kinetic resolution of racemic esters catalyzed by Pseudomonasfluorescens esterase (PFE) [50]. Using a mutator strain and by screening very small libraries, low improvement in enantioselectivity was... 

In another study a hyperthermophilic esterase from Aeropyrum pemix K1 (APE1547) was used as a catalyst in the hydrolytic kinetic resolution of rac-3-octanol acetate [53]. Following a single round of epPCR, a mutant displaying a 2.6-fold increase in enantioselectivity was identified having five amino acid substitutions, which were shown to be spatially distal to the catalytic center. 

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]. 

Syntheses of aliphatic polyesters by fermentation and chemical processes have been extensively studied from the viewpoint of biodegradable materials science. Recently, another approach to their production has been made by using an isolated lipase or esterase as catalyst via non-biosynthetic pathways under mild reaction conditions. Lipase and esterase are enzymes which catalyze hydrolysis of esters in an aqueous environment in living systems. Some of them can act as catalyst for the reverse reactions, esterifications and transesterifications, in organic media [1-5]. These catalytic actions have been expanded to... 

Caturla, F., Enjo, J., Bemabeu, M. C. and Le Serre, S. (2004). New fluorescent probes for testing combinatorial catalysts with phosphodiesterase and esterase activities. Tetrahedron 60, 1903-1911. 

In summary, the formation of optically active compounds through hydrolysis reactions is dominated by biocatalysis mainly due to the availability and ease of use of a wide variety of esterases, lipases and (to a lesser extent) acylases. Epoxide ring-opening (and related reactions) is likely to be dominated by salen-metal catalysts while enzyme-catalysed nitrile hydrolysis seems destined to remain under-exploited until nitrilases or nitrile hydratases become commercially available. 

Another reactive site, called the T-site, makes a modest contribution to the overall hydrolytic activity of the protein (ca. 11%), and a lysine residue has been suggested as the catalyst. The position of the T-site might be in the subdomain IIA of HSA (Fig. 3.17), since there is evidence that Lys220 in sub-domain IIA could belong to an esterase site [119][120],... 

It is important to note that acetylsalicylic acid and some 4-nitrophenyl esters are quite reactive species that easily acylate nucleophiles. With such compounds, albumin indeed behaves as a catalyst, but it is simultaneously a target, and the term esterase-like activity can only be understood with this restriction in mind. 

Y. Morimoto, Y. Terao, K. Achiwa, Enzymes and Catalysts. I. Pig Esterase-Catalyzed Hydrolysis of Heterocyclic Diesters , Chem. Pharm. Bull. 1987, 35, 2266-2271. 

Chemical reactions enhanced by catalysts or enzymes are an integral part of the manufacturing processes for the majority of chemical products. The total market for catalysts and enzymes amounts to 11.5 billion (2005), of which catalysts account for about 80%. It consists of four main applications environment (e.g., automotive catalysts), 31% polymers (e.g., polyethylene and polypropylene), 24% petroleum processing (e.g., cracking and reforming), 23% and chemicals, 22%. Within the latter, particularly the catalysts and enzymes for chiral synthesis are noteworthy. Within catalysts, BINAPs [i.e., derivatives of 2,2 -bis(diphenylphosphino) -1, l -bis-l,l -binaphthyl) have made a great foray into chiral synthesis. Within enzymes, apart from bread-and-butter products, like lipases, nitrilases, acylases, lactamases, and esterases, there are products tailored for specific processes. These specialty enzymes improve the volumetric productivity 100-fold and more. Fine-chemical companies, which have an important captive use of enzymes, are offering them to third parties. Two examples are described here ... 

The use of enzymes and whole cells as catalysts in organic chemistry is described. Emphasis is put on the chemical reactions and the importance of providing enantiopure synthons. In particular kinetics of resolution is in focus. Among the topics covered are enzyme classification, structure and mechanism of action of enzymes. Examples are given on the use of hydrolytic enzymes such as esterases, proteases, lipases, epoxide hydrolases, acylases and amidases both in aqueous and low-water media. Reductions and oxidations are treated both using whole cells and pure enzymes. Moreover, use of enzymes in sngar chemistiy and to prodnce amino acids and peptides are discnssed. 

The optimum yield of a condensation product is obtained at the pH where Ka has a maximum. For peptide synthesis with serine proteases this coincides with the pH where the enzyme kinetic properties have their maxima. For the synthesis of penicillins with penicillin amidase, or esters with serine proteases or esterases, the pH of maximum product yield is much lower than the pH optimum of the enzymes. For penicillin amidase the pH stability is also markedly reduced at pH 4-5. Thus, in these cases, thermodynamically controlled processes for the synthesis of the condensation products are not favorable. When these enzymes are used as catalysts in thermodynamically controlled hydrolysis reactions an increase in pH increases the product yield. Penicilhn hydrolysis is generally carried out at pH about 8.0, where the enzyme has its optimum. At this pH the equiUbrium yield of hydrolysis product is about 97%. It could be further increased by increasing the pH. Due to the limited stability of the enzyme and the product 6-aminopenicillanic acid at pH>8, a higher pH is not used in the biotechnological process. 

The findings that, both in ester and amide cleavage, an alkaline-earth metal ion is still catalytically active when complexed with a crown ether, and that a fraction of the binding energy made available by coordinative interactions with the polyether chain can be translated into catalysis, provide the basis for the construction of supramolecular catalysts capable of esterase and amidase activity. 

For reviews of esler hydrolysis catalyzed by pig liver esterase, see Zhu Tedford Tetrahedron 1990, 46. 6587-6611 Ohno Otsuka Org. React. 1989, 37, 1-55. For reviews of enzymes as catalysts in synthetic organic chemistry, sec Wong Chemtracts Org. Chem. 1990, 3, 91-111, Science 1989, 244, 1145-1152 Whitesides Wong Angew. Chem. Int. Ed. Engl. 1985, 24, 617-638 [Angew. Chem. 97. 617-638). 

In enzymes, the most common nucleophilic groups that are functional in catalysis are the serine hydroxyl—which occurs in the serine proteases, cholinesterases, esterases, lipases, and alkaline phosphatases—and the cysteine thiol—which occurs in the thiol proteases (papain, ficin, and bromelain), in glyceraldehyde 3-phosphate dehydrogenase, etc. The imidazole of histidine usually functions as an acid-base catalyst and enhances the nucleophilicity of hydroxyl and thiol groups, but it sometimes acts as a nucleophile with the phos-phoryl group in phosphate transfer (Table 2.5). 

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