Substrate spectrum

In general, Oatp/OATP substrates are mainly anionic amphipathic molecules with high molecular weight ( 450) that under normal physiological conditions are bound to proteins (mostly albumin). More specifically, compounds with a steroid nucleus (e.g., bile salts, steroid hormones, and their conjugates) or small linear and cyclic peptides are likely candidates to be transported by certain Oatps/OATPs. These are 

Drugs dexamethasone, enalapril (214 pM), fexofenadine (32 pM), gadoxetate (3.3 mM), ouabain (1.7-3 mM), pravastatin (30 pM), temocaprilat (47 pM), bosentan Other organic anions monoglucuronosyl bilirubin, BSP (1-3 pM), BSP-DNP-SG (408 pM), E3040 glucuronide 

Organic cations APD-ajmalinium, N-methylquinidine, rocuronium Toxins ochratoxin A (17-29 pM) 

Bile salts taurocholate (10/31 pM) Hormones and their conjugates DHEAS (8/ 8pM), E2l7 3G (35/45 pM), E-3-S (12/ 

Bile salts cholate (46 pM), glycocholate (40 pM), taurocholate (35 pM), TCDCA (12 pM), TUDCA (17 pM) 

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The L-threonine (EC 4.1.2.5), D-threonine (EC 4.1.2.-) or L-allothreonine aldolases (EC 4.1.2.6 synonymous to S1IMT) can be used for resolution of racemic (allo)threonine mixtures by highly selective cleavage of the unwanted isomers42, but can also efficiently direct the anabolic pathways. The substrate spectrum includes propanal, butanal and dodecanal43. 

Metallo-enzymes belonging to group 3 naturally show a very broad substrate spectrum including all (3-lactams excqrt monobactams and are not inhibited by clavulanic acid, but by complexing agents, like EDTA. This can only be exploited for diagnostic purposes. 

Antibiotic Resistance. Figure 1 According to Bush, Jacoby and Medeiros [2] four molecular classes of (3-lactamases can be discriminated based upon biochemical and molecular features. Classes 1, 2, and 4 included serine-proteases, while metallo enzymes are included in class 3. The substrate spectrum varies between different subclasses and the corresponding genes can be part of an R-plasmid leading to a wider distribution or are encoded chromosomally in cells of specific species. 

The class A enzymes have Mx values around 30,000. Their substrate specificities are quite variable and a large number of enzymes have emerged in response to the selective pressure exerted by the sometimes abusive utilization of antibiotics. Some of these new enzymes are variants of previously known enzymes, with only a limited number of mutations (1 4) but a significantly broadened substrate spectrum while others exhibit significantly different sequences. The first category is exemplified by the numerous TEM variants whose activity can be extended to third and fourth generation cephalosporins and the second by the NMCA and SME enzymes which, in contrast to all other SXXK (3-lactamases, hydrolyse carbapenems with high efficiency. Despite these specificity differences, the tertiary structures of all class A (3-lactamases are nearly superimposable. 

It carried out dechlorination of tetra- and trichloroethene to di-l,2-dichloroethene, and had a substrate spectrum that included tetrachloromethane, hexachloroethane, and 1,1,1-trichloro-2,2,2-triflnorarethane althongh the products from these were not apparently identified (Maillard et al. 2003). 

The 3-ketothiolase has been purified and investigated from several poly(3HB)-synthesizing bacteria including Azotobacter beijerinckii [10], Ral-stonia eutropha [11], Zoogloea ramigera [12], Rhodococcus ruber [13], and Methylobacterium rhodesianum [14]. In R. eutropha the 3-ketothiolase occurs in two different forms, called A and B, which have different substrate specificities [11,15]. In the thiolytic reaction, enzyme A is only active with C4 and C5 3-ketoacyl-CoA whereas the substrate spectrum of enzyme B is much broader, since it is active with C4 to C10 substrates [11]. Enzyme A seems to be the main biosynthetic enzyme acting in the poly(3HB) synthesis pathway, while enzyme B should rather have a catabolic function in fatty-acid metabolism. However, in vitro studies with reconstituted purified enzyme systems have demonstrated that enzyme B can also contribute to poly(3HB) synthesis [15]. 

In adopting the ANG approach (Chap. 4), only a few modifications are required, which are mainly concerned with the substrate spectrum being discrete rather than continuous. The conceptual set-up is portrayed in Fig. 7.4. 

To ensure the specificity of the signal, it will always be very helpful to test a unique feature of the carrier under investigation, such as specific inhibition, dependence on anions/cations/protons or trans-activation by another substrate. Sodium dependency, for example, can be tested by replacement with N-methyl-D-glucamine, whereas choline chloride as substitute of sodium is not recommended, since it may influence the membrane potential. In light of the recent finding that many transport proteins display an overlapping substrate spectrum, such specificity controls should receive adequate appreciation. 

AspAT has been shown to display a broad substrate spectrum. This chemoenzymatic procedure is, therefore, a very convenient way to prepare a variety of L-2,4-syn Glu analogues substituted at the 4-position by alkyl or functionalized substituents. Moreover, this catalyst has been used for the preparation of 4,4-disubstituted ° and (25,3R)-3-methyl Glu derivatives, as well as the cyclobutane analogues LCBG II-IV. The different Glu analogues prepared to date using this methodology are reported in Figure 10.1. 

Further success in increasing yield and concentration of 1,3-PD is expected from the application of metabohc engineering and recombinant DNA technology, especially with respect to extending the substrate spectrum to use cheaper and abundant substrates such as glucose and starch [12,13]. 

The selection of appropriate microorganisms is a possible way to improve the correlation between BOD and BODj [16,53]. The prerequisite for the use of microorganisms for BOD-sensors is a wide substrate spectrum. Therefore several samples of activated sludge from different wastewater plants were investigated [ 13,14]. One problem with an activated sludge based biosensor is the variability of sensor response with time. These BOD-sensors with an undefined variety of microbial species revealed no reproducible results. For that reason, BOD-sensors were developed using various types of defined cultures of microorganisms (Table 1). 

Yeasts are specially suitable, because they are able to use a wide substrate spectrum combined with a wide measuring range. 

Another way to increase the substrate spectrum of BOD-sensors is to combine various types of microorganisms, which exhibit different substrate sensitivities. Such a combined sensor containing BadHus subtilis and B. licheniformis [44], Citrobacter sp., and Enterobacter sp. [45], or the bacterium Rhodococcus erythropolis and the yeast Issatchenkia orientalis is used in a commerciahzed BOD-sensor system [11, 46]. In these biosensors, the substrate sensitivities of both species associated, as shown by Riedel and Uthemann [54]. 

Through investigations of the reaction in Scheme 2.1.3.3, the substrate spectrum was unraveled [17]. Various aromatic aldehydes based on the ketimines 5a, 6a,... 

Substituted [2.2]Parac fciopbane Derivatives as Efficient Ligands 211 Table 2.1.3.2 Substrate spectrum for the phenyl transfer to imines. ... 

R) -specific ADH from L. kefir was used for the reduction of various ketones to the corresponding secondary alcohols. Aliphatic, aromatic, and cyclic ketones as well as keto esters were accepted as substrates. The activities achieved with several substrates were compared with the activity obtained with the standard substrate of ADH, acetophenone (Fig. 2.2.4.4). As the figure shows, recombinant LK-ADH has a very broad substrate spectrum, including many types of ketones. 

The substrate spectrum of SuSyl from yeast is well documented for a variety of acceptors [24, 29, 30]. In the series of ketoses we concluded that SuSyl favors the 3S,4R configuration because L-sorbose 4 and D-xylulose 5 are accepted and D-tagatose 6, D-psicose 7, and D-sorbose 8 are not substrates (Fig. 2.2.6.1 and... 

Preliminary investigations on the substrate spectrum of the SllA mutant of SuSyl expressed in yeast reveal L-glucose 29 and L-rhamnose 30 as new substrates, as well as D-xylulose 5 with a relative activity of 112%. Most interestingly, both mutants accept D-psicose and L-fucose as new acceptor substrates. 

L-Pipecolinic acid-derived formamides have been developed as highly efficient and enantioselective Lewis basic organo-catalysts for the reduction of IV-arylimines with trichlorosilane. High isolated yields and enantioselectivities up to 96% are obtained under mild conditions with a large substrate spectrum.365... 

In summary, much information has been gathered by different methods, but there is still room for improvement of the substrate spectrum of the diketopiperazine catalyst 1 and for detailed understanding of the mechanism - and thus predictability - of this fairly complex heterogeneous catalyst system. Nevertheless, enantiomerically pure cyanohydrins - prepared with the aid of 1 - have already been used for synthesis of several natural product (and other) target molecules... 

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