Enzyme inhibitors commercial applications

Many peptidomimetics derived from the design of TSA inhibitors, molecules designed according to the hypothesis provided by Pauling (77) and implemented by Wolfenden (78,79). TSA protease inhibitors are stable analogs of the tetrahedral intermediate for peptide bond hydrolysis that inhibit the enzyme (Fig. 15.18). The first successful commercial application was the development of captopril (38) by Ondetti et al. (80), and many applications have been reported over the past quarter century. 

Isolated RNA may contain tissue enzyme inhibitors and genomic DNA that result in reduced RT and PCR reaction efficiencies and generate unreliable and wrong quantification results. While this is not a problem for some applications, the tremendous amplification power of kinetic PCR may result in even the smallest amount of DNA contamination interfering with the desired specific amplification. To confirm the absence of residual DNA, a minus-RT should be included. Additionally it may be necessary to treat the RNA sample with commercially available RNAse-free DNAse, to get rid of residual DNA. Furthermore, the design of the PCR product should incorporate at least one exon to exon splice junction to allow a product obtained from the cDNA to be distinguished from genomic DNA contamination. 

Commercial sources of enzymes are any living organism, i.e., animals, plants, and microbes. These naturally occurring enzyme sources are quite readily available for the commercial productivity of sufficient quantities for food applications and/or other industrial uses. Table 4.1 shows some important representative industrial enzymes from animal, plant, and microbial sources. Of the number of these industrial enzymes, the majority (more than half come from fungi and yeast and a third from bacteria) come from microorganisms and the reminder, a minority, from animals (8%) and plants (4%). A number of enzymes have found use, also, in chemical analyses and medical diagnosis. However, enzymes from microbes are preferred than from animals and plants because (1) they are cheaper to produce (2) they are more predictable and controllable (3) they are reliable supplies of raw materials of constant composition and (4) plant and animal tissues contain more harmful materials (phenolics, inhibitors, etc.)... 

The problems of choosing one of the several commercial enzymes for a specific food system application are (1) wide ranges in enzyme activities assayed by different methods, (2) batch to batch variability, (3) different pH and temperature profiles depending on the source, (4) activators or inhibitors necessary for the reaction, and (5) compatibility of combining two or more enzymes. ... 

The only other application of hydroformylation applied to the synthesis of a pharmaceutical intermediate on a commercial scale has recently been reported. The synthesis of (S)-allysine ethylene acetal, an intermediate in the manufacmre of angiotensin I-converting enzyme (ACE) and neutral endopeptidase (NEP) inhibitors, was reported by researchers at Dr. Reddy s and Chirotech using a combination of... 

In the world market, more than 90% of commercial biosensors are enzymatic, in particular, those that measure glucose, used by diabetics [79]. This kind of biosensors is very useful because if immobilized enzymes are sensitive to certain pollutants, these analytes can be easily measured. For example, biosensors based on the inhibition of acetylcholinesterase detect phosphorus insecticides and other inhibitors [80]. A comprehensive analysis showed that the developed enzymatic biosensors demonstrated reproducible, stable, and fast responses to the substrates to be measured. Unfortunately, the application of these biosensors can be restricted because of the dramatic decrease in the sensor response at increasing buffer capacity and ionic strength, pH-dependence of the enzyme kinetics, and cosubstrate limitation of the measured enzymatic reaction rate (the glucose sensor) [79]. Recently, Soldatkin et al. reported a complete review of some biopolymers used in enzymatic... 

The most important application of enzymatic transamination has recently been demonstrated for the synthesis of SItagliptin (Januvia ) [48], a commercial DPP-4 inhibitor from Merck for the treatment of diabetes. Merck and Codexis started from a TA enzyme with... 

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