Synthetic enzyme models

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]. 

Room temperature phosphorescence which can occur in mixed organic media is observed in synthetic enzyme model surfactant systems.The effect of pH on the p-aminobenzoic acid photosensitized dimerization of free thymine base shows that the triplet state is involved in this reaction. 8 The nature of the... 

Studies on the oxygen activation mechanisms by new heme enzymes using hemoprotein mutants and synthetic heme models 96YGK1046. 

Homochiral molecules readily available from inexpensive sources are useful synthetic building blocks and chiral auxiliaries. 1,4-01-0-benzyl-L-threitol has been used in construction of homochiral crown ethers that are useful as enzyme model systems. Topologically controlled diastereoselective delivery of the Simmons-Smith reagent for 2-cycloalken-l-one 1,4-d1-0-benzyl-L-threitol ketals was recently reported. ... 

The biochemical model contains the pathways of the enzymatic reactions in the synthetic routes. Model can be constructed for each alkaloid. Eigure 75 presents biochemistry model of Catharantus alkaloids. The most important enzymes on this model are TDC (tryptophan decarbocylase), GlOH (geraniol 10-hydroxylase) and SS (strictoside synthase). NADPH+, PO (Peroxidase), O (oxidase) and NADH+ are all active in different Catharantus alkaloid formations. The biochemical models are subject to both qualitative and quantitative alkaloid... 

The International Union of Biochemistry and Molecular Biology recommends that the term peptidase be used synonymously with the term peptide hydrolase (IUBMB, 1992). Thus, in this unit the term peptidase is used in reference to any enzyme that catalyzes the hydrolysis of peptide bonds, without distinguishing between exo- and endopeptidase activities. Peptidases may be assayed using native or modified proteins, peptides, or synthetic substrates. In this unit, the focus is on assays based on the hydrolysis of common, commercially available, protein substrates. Thus, the assays are not intended to be selective for a given peptidase they are designed to provide estimates of overall peptidase activity. Other units in this publication focus on synthetic or model substrates, which can be designed for the measurement of specific endo- and/or exopeptidase activities. 

Studies with synthetic P450 enzyme models have already been mentioned to contribute to the understanding of the mechanisms of P450 action and to provide information on the possible structure and electronic nature of iron porphyrins as intermediates of the catalytic cycle. 

The literature of metabolism in proteinoids and proteinoid microspheres is reviewed and criticized from a biochemical and experimental point of view. Closely related literature is also reviewed in order to understand the function of proteinoids and proteinoid microspheres. Proteinoids or proteinoid microspheres have many activities. Esterolysis, decarboxylation, animation, deamination, and oxido-reduction are catabolic enzyme activities. The formation of ATP, peptides or oligonucleotides is synthetic enzyme activities. Additional activities are hormonal and inhibitory. Selective formation of peptides is an activity of nucleoproteinoid microspheres these are a model for ribosomes. Mechanisms of peptide and oligonucleotide syntheses from amino acids and nucleotide triphosphate by proteinoid microspheres are tentatively proposed as an integrative consequence of reviewing the literature. 

The most promising direction for enzyme modeling is to synthetically mimick the nature of the binding site and the active site in terms of the close similarity of catalytic groups, stereochemistry, interatomic distances and the mechanism of the action of the enzyme. Mimicking of the proton-transfer relay proposed for the mechanism of the action of chymotrypsin is a brilliant example of such work (D Souza and Bender, 1987 and references therein). The miniature organic model of chymotrypsin built on the basis of cyclodextrin and the mechanism of hydrolysis m-tert-butylphenyl acetate is presented in Fig. 6.9. 

As in the case of horseradish peroxidase, several synthetic metalloporphyrins in the presence of H2O2 have been found to be potent catalysts for the chemiluminescent oxidation of luminol or isoluminol. The microperoxidases, mainly MP8 and MPll, have been shown to act as functional peroxidase enzyme models. " However, they are readily inactivated within one min of catalytic turnover, and incorporation into a molecular sieve... 

Synthetic complexes modeling a-keto carboxylate-dependent enzymes have played a key role in furthering our understanding of these enzymes. Several [Fe (L)(a -keto acid)] complexes have been reported as functional models using tetradentate and tridentate ligands. All of the model complexes that react with O2 afford quantitative yields of the decarboxylated a-keto acid, but in only two cases was the active oxidant trapped. Intermolecular olefin epoxidation has been observed in the case of [Fe (Tp )(BF)j complex. This complex reacts with O2 to form a species capable of stereospecific oxidation of cA-stilbene to its oxide as the product. However trans -stilbene is not epoxidized, suggesting that the active oxidant is capable of steric discrimination. 

V. Critique of the Use of Synthetic Polymers and Micelles as Enzyme Models... 

Studies of a synthetic analog model system provide evidence for the mechanism s plausibility. A simple synthetic ligand binds zinc through four nitrogen atoms (compared with three histidine nitrogen atoms in the enzyme),... 

---