Relative specificity

Metrifonate [52-68-6] (24) is itself not an AChE inhibitor, but is none2ymaticaIly converted into an active irreversible inhibitor of the en2yme. The compound is relatively specific for AChE over butyrylcholinesterase (135) and the irreversible nature of its inhibition gives rise to an extended duration of action. Some clinical experience has been gained through its use to treat schistosomiasis (136,137) and it is undergoing clinical evaluation for AD. 

In the treatment of poisoning by lead or other metal ions, higher concentrations of chelant can be safely obtained in humans by administering Na2CaEDTA rather than Na EDTA. The metal ion is bound by displacing small amounts of Ca " that the body can tolerate. Use of Na EDTA would result in calcium chelation and thus serious depletion of calcium in the body fluids (44). Removal of iron in Cooley s anemia is accompHshed by using chelants that are relatively specific for iron (45). 

The changes in the specificity constants, on the other hand, were as expected from the predictions. The ratio of the fccat/ m values for the Arg and Lys substrates (last column in Table 11.1) gives a measure of the relative specificities. This ratio decreases for the Ala 226 mutant and increases for the Ala 216 mutant as predicted. However, the changes in these values depend not... 

Determine the amount of wet cake obtained from filtering 10 m of suspension with a relative specific weight of 1.12. The suspension is 20% by weight solids and the cake wetness is 25%. 

Heat transfer between gas and sohds is exceedingly hard to measure because it is so rapid. Although the coefficient is low, the available surface area and the relative specific heat of solid to gas are so large that temperature equilibration occurs almost instantaneously. Experiments on injection of argon plasmas into fluidized beds have shown quenching rates of up to fifty million degrees Kelvin per second. Thus, in a properly designed bed, gas to solids heat transfer is not normally a matter of concern. 

In recent years, biochemists have developed an arsenal of reactions that are relatively specific to the side chains of particular amino acids. These reactions can be used to identify functional amino acids at the active sites of enzymes or to label proteins with appropriate reagents for further study. Cysteine residues in proteins, for example, react with one another to form disulfide species and also react with a number of reagents, including maleimides (typically A ethylmaleimide), as shown in Figure 4.11. Cysteines also react effectively... 

Candidate protease inhibitor drugs must be relatively specific for the HIV-1 protease. Many other aspartic proteases exist in the human body and are essential to a variety of body functions, including digestion of food and processing of hormones. An ideal drug thus must strongly inhibit the HIV-1 protease, must be delivered effectively to the lymphocytes where the protease must be blocked, and should not adversely affect the activities of the essential human aspartic proteases. 

Table 7.14 Relative specific scaling rale constant for binary nickel alloys at 900°C ...

Endothelial NO Synthase (eNOS) expression is relatively specific for endothelial cells. However, the isozyme has also been detected in certain neurons of the brain, in syncytiotrophoblasts of human placenta and in LLC-PKi kidney tubular epithelial cells. 

At the practical level, an ideal mechanistic biomarker should be simple to use, sensitive, relatively specific, stable, and usable on material that can be obtained by nondestructive sampling (e.g., blood or skin). A tall order, no doubt, and no biomarker yet developed has all of these attributes. However, the judicious use of combinations of biomarkers can overcome the shortcomings of individual assays. The main point to emphasize is that the resources so far invested in the development of biomarker technology for environmental risk assessment has been very small (cf the investment in biomarkers for use in medicine). Knowledge of toxic mechanisms of organic pollutants is already substantial (especially of pesticides), and it grows apace. The scientific basis is already there for technological advance it all comes down to a question of investment. 

Since PD is caused by a relatively specific degeneration of the DA nigrostriatal tract and as there are specific toxins, for DA neurons, i.e. 6-OHDA and MPTP, it should be possible to produce appropriate experimental models. Certainly both toxins cause rotational behaviour in rats (Fig. 7.7) but no rodent shows a syndrome suggestive of PD. Tremor and akinesia can be seen, however, in primates after such toxins and these are being more widely used in experimental studies of PD and drug evaluation. Reserpine causes a depletion of all brain monoamines and produces motor defects in rats, which, even if not PD-like, do respond to DA manipulation. 

No overall reduction in cholinergic muscarinic receptors was found but recent studies with relatively specific ligands show a loss of presynaptic M2 receptors, in keeping with the loss of terminals, but no reduction in postsynaptic Mi receptors. Some acetylcholinesterase is found in plaques. 

The data in Table I are also significant in terms of the type of analysis to determine the presence of NDMA. In all cases analysis was done using gas chromatography coupled with a Thermal Energy Analyzer, a sensitive, relatively specific nitrosamine detector (12). Further, in six of the studies, the presence of NDMA in several samples was confirmed by gas chromatography-mass spectrometry (GC-MS). The mass spectral data firmly established the presence of NDMA in the beer samples. 

Tyrosine kinase inhibitor relatively specific for the tyrosine kinase coded for by the bcr-abl translocation in CML patients... 

Table IX. Relative Specific Activities of Products from Treatments of Lemons with...

Schmidt If you are looking for a compound that is relatively specific for Gl, there is a chemotherapeutic agent being introduced into clinical trials called flavupiridol, which has preferential effects on Gl and leads to degradation of cyclin D1 in breast cancer cells. 

The data presented in Table 3, which includes the amino acid composition of baker s yeast and Candida krusei cytochrome c for comparison, show that Ustilago and Neurospora cytochrome c contain the same number of total residues. In seven instances, the number of residues of a particular amino acid/mole are identical. Thus, even in the absence of a sequence for the Ustilago cytochrome it can be concluded that this protein, unlike the siderochromes, has suffered little alteration in the progression from the Ascomycetes to the Basidiomycetes. This can be ascribed to the varying function of the two types of molecules. Cytochrome c must fit into a relatively specific slot bounded by a reductase and an oxidase and it has hence evolved much more slowly than the more freely acting transport agents where the specificity constraints are less demanding. 

Figure 8.10 Relative specific activity of Y296 mutations of Alcaligenes faecalis Nitl650 nitrilase for conversion of racemic 2-chloromandelonitrile Y296A (A), Y296F (F), Y296C (C), Y296G (G), Y296N (N), Y296T (T), and Y296S (S)...

Figure 8.11 Relative specific activity of Alcaligenes faecalis Nitl650 nitrilase ( ) and Y296C mutant nitrilase ( ) for conversion of unsubstituted and substituted mandelonitrile mandelonitrile (MN), 2-chloromandelonitrile (2-CMN), 3-chloromandelonitrile (3-CMN), 4-chlormandelonitrile (4-CMN), 4-bromomandelonitrile (4-BMN), and 4-methylmandelonitrile (4-MeMN)...

Table 5.1 lists a number of SG and PB markers, and indicates the relative specificity of each reagent for SGs or PBs. This is only a partial list of known SG and PB markers, focusing on some that are broadly useful and for which antibodies are readily available. The staining patterns obtained using some of these antibodies are shown in Fig. 5.1. 

Acetic anhydride is the only monocarboxylic acid anhydride that is important in modification reactions. The acetylation of the amino groups of proteins can be made relatively specific if the reaction is done in saturated sodium acetate, since the o-acetyltyrosine derivative is unstable to an excess of acetate ions (Fraenkel-Conrat, 1959). The tyrosine derivative rapidly hydrolyzes in alkaline reaction conditions, even in the absence of added acetate buffer (Uraki et al., 1957 Smyth, 1967). Treatment with hydroxylamine also cleaves any o-acetyltyrosine modifications, forming acetylhydroxamate, which can be followed by its purple complex with Fe3+ at 540 nm... 

In addition to the relatively specific inhibitors listed in this table, there are a number of compounds, particularly the methylxanthines (e.g. theophylline, isobutylmethylxanthine (IBMX), papaverine, caffeine), that inhibit most major forms of PDE except the newer forms). SCH51866 is not selective and inhibits PDE1, PDE5, PDE9, and PDE10 with IC50 values shown. 

Isopropylbenzene (A) is alkylated with propylene (P) using HF catalyst. The mono (B), di (C), tri (D) and tetra (E) derivatives are formed. Relative specific rates are given by Rodiguin Rodiguina (Consecutive Chemical Reactions, 1964) for the case of a large excess of propylene which makes the reactions pseudo first order. The relative specific rates used here are kx = 1.0, k2 = 0.5, k3 = 0.3 and k4 0.2. The system of linear differential... 

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