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Hydrolysis of the Amide Bond

The generally appliable hydrolytic methods have been selected from the numerous strategies of enzymatic amino acid synthesis [92, 97-103]. They also are useful tools for the preparation of enantiomerically pure nonnatural amino acids [104], not only for industrial needs but also for research on a laboratory scale. [Pg.52]

However, there is a hmitation to the majority of these methods the a-carbon atom bearing the amino group must not be fully substituted, since such bulky substrates are generally not accepted by hydrolases. Thus, optically pure a-methyl or a-ethyl amino acids are generally not accessible by these methods, although some exceptions are known [105, 106]. [Pg.52]

Carbonic anhydrase - an enzyme termed for its ability to catalyze the hydration of carbon dioxide forming hydrogen carbonate - can also be employed. In contrast to the above-mentioned biocatalytic systems, it exhibits the opposite enantiopre-ference by hydrolyzing the D-N-acylamino acid esters [123]. [Pg.54]

the L-amino acids thus formed are separated from the unreacted o-amino acid amide by the difference in solubility in various solvents at various pH. After separation, unreacted D-amino acid amides can be recycled via base-catalyzed racemization of the corresponding Schiff-base intermediates in a separate step [131]. Since amino acid amides are less susceptible to spontaneous chemical hydrolysis in the aqueous environment than the corresponding esters, the products which are obtained by this method are often of higher optical purities. [Pg.55]

R = alkyl, aryl Acyl = acetyl, chloroacetyl, benzyloxycarbonyl [Pg.56]


Deamidation of soy and other seed meal proteins by hydrolysis of the amide bond, and minimization of the hydrolysis of peptide bonds, improves functional properties of these products. For example, treatment of soy protein with dilute (0.05 A/) HCl, with or without a cation-exchange resin (Dowex 50) as a catalyst (133), with anions such as bicarbonate, phosphate, or chloride at pH 8.0 (134), or with peptide glutaminase at pH 7.0 (135), improved solubiHty, whipabiHty, water binding, and emulsifying properties. [Pg.470]

The main application of the enzymatic hydrolysis of the amide bond is the en-antioselective synthesis of amino acids [4,97]. Acylases (EC 3.5.1.n) catalyze the hydrolysis of the N-acyl groups of a broad range of amino acid derivatives. They accept several acyl groups (acetyl, chloroacetyl, formyl, and carbamoyl) but they require a free a-carboxyl group. In general, acylases are selective for i-amino acids, but d-selective acylase have been reported. The kinetic resolution of amino acids by acylase-catalyzed hydrolysis is a well-established process [4]. The in situ racemization of the substrate in the presence of a racemase converts the process into a DKR. Alternatively, the remaining enantiomer of the N-acyl amino acid can be isolated and racemized via the formation of an oxazolone, as shown in Figure 6.34. [Pg.146]

PARACEST agents with a response to enzymatic activity have also been reported. Pagel et al. used a Tm1 DOTA monoamide complex containing a peptide chain which is hydrolyzed by the Caspase-3 enzyme (204,205). Following enzymatic cleavage, the PARACEST effect originating from the amide proton disappears due to the hydrolysis of the amide bond. [Pg.104]

N-Methyl substitution does not seem to influence dramatically the hydrolysis of the amide bond. Indeed, a similar relationship between hydrolysis and chain length has been described for unsubstituted aliphatic amides... [Pg.107]

The hydrolysis of the amide bond in chloramphenicol (4.26), which liberates dichloroacetic acid (4.27) and the primary amine (4.28), has been shown in bacteria, rodents, and humans [13-15]. In the microsomal fraction of guinea pig liver, moreover, the enzyme responsible for hydrolysis has been identified as one of the B-type carboxylesterase isoenzymes [16]. [Pg.108]

Other examples of secondary benzamides include the therapeutic class of orthopramides, which are, again, markedly resistant to hydrolysis. Thus, hydrolysis of the amide bond is a minor metabolic pathway in humans for the antiemetic drug metoclopramide (4.76) [49]. Clebopride (4.77), an anti-dopaminergic agent, was found to be hydrolyzed to a limited extent in rabbit liver homogenates and in dogs to 4-amino-5-chloro-2-methoxybenzoic acid (4.78) and to the amine 4.79 [48] [50], Attempts to detect in vivo formation of this metabolite in rats, rabbits, or humans were not successful [50],... [Pg.120]

Other orthopramides have been shown to be resistant to in vivo hydrolysis. Thus, the gastrokinetic drug cisapride (4.80) was not hydrolyzed after oral administration to dogs and humans [51]. Similarly, sulpiride (4.81), an antidepressant and antipsychotic drug, did not undergo hydrolysis in humans and laboratory animals. These compounds are metabolized by other routes, and hydrolysis of the amide bond, when it occurs at all, is only a minor pathway. [Pg.120]

Methylation in both ortho-positions on the aniline ring appears to impede hydrolysis of the amide bond. Thus, 2,4,6-trimethylacetanilide (4.105) was not hydrolyzed by rat liver homogenates, perhaps due to steric hindrance by the 2- and 6-Me groups [71]. Similarly, the amide bond of the hypocholes-terolemic agent 2,2-dimelhyl-A-(2,4,6-trimethoxypheiiyl )dodccanamidc... [Pg.128]

Hydrolysis of the amide bond generally leads to inactivation of the substrate and accelerates excretion of the products. In the case of aminoacyl-anilides, however, such hydrolysis may represent a pathway of toxification, since it liberates aromatic amines, which are potentially hematotoxic, nephrotoxic, hepatotoxic, and/or carcinogenic. [Pg.137]

The intrinsic inertness of the peptide bond is demonstrated by a study of the chemical hydrolysis of N-benzoyl-Gly-Phe (hippurylphenylalanine, 6.37) [67], a reference substrate for carboxypeptidase A (EC 3.4.17.1). In pH 9 borate buffer at 25°, the first-order rate constant for hydrolysis of the peptide bond ( chem) was 1-3 x 10-10 s-1, corresponding to a tm value of 168 y. This is a very slow reaction indeed, confirming the intrinsic stability of the peptide bond. Because the analytical method used was based on monitoring the released phenylalanine, no information is available on the competitive hydrolysis of the amide bond to liberate benzoic acid. [Pg.287]

The cleavage mechanism of the caspases is shown schematically in Fig. 15.5. They use a typical protease mechanism with a catalytic diad for cleavage of the peptide bond. The nucleophilic thiol of an essential Cys residue forms a covalent thioacyl bond to the substrate during the catalysis. The imidazole ring of an essential histidine is also involved in catalysis and this facilitates hydrolysis of the amide bond in the sense of an acid/base catalysis. [Pg.459]

Photolysis of l,6-dimethylpyridazinium-3-olate (137 R = R = Me, R = R" = H) in water gives 2,6-diniethylpyridazin-3-one (140), whereas irradiation in acetonitrile solution gives the fused diaziridine 141 which is converted into compound 140 by water. This transformation (141 - 140) probably involves initial hydrolysis of the amide bond (see Section III,B,7). ... [Pg.26]

The term / -lactamase denotes an enzyme which catalyzes the hydrolysis of the amide bond in the /3-lactam ring of 6-amino-penicillanic acid (6-APA) or 7-amino-cephalosporanic acid (7-ACA) and of their A-acyl derivatives (2). Such derivatives are commonly referred to as penicillins [Fig. 1 (I) and cephalosporins Fig. 1 (III), (V), and (VII)], respectively. There is no evidence that any bond other than the amide bond in the intact nucleus of penicillin or cephalosporin is broken by the... [Pg.25]

Each reaction brings about hydrolysis of the amide bond. Each product is shown as it would exist under the specified reaction conditions. [Pg.53]

Hydrolysis of the amide bond in 2,4-dinitroacetanilide furnishes the desired 2,4-dinitroaniline. [Pg.611]

The two substances, sphingosine and cerebronic acid, that are formed along with D-galactose arise by hydrolysis of the amide bond. [Pg.741]

Phosphonopeptides containing a transition state analog of the hydrolysis of the amide bond represent another attractive approach for the preparation of proteolitically stable peptides (10,30,31). In addition to increased stability, incorporation of a phosphonate moiety into the peptide sequence provides access to additional binding interactions within the transition-state conformation of the enzyme/substrate complex (13). This peptidomimetic approach is used to design very effective protease inhibitors (31-34). As in the case... [Pg.230]

Further steps will be taken in order to implement bioconversion of the nitro group as well as biochemical glucuronidation and glutathionylation of the drug. Since hydrolysis of the amide bond was found to be caused by the action of glutathione, glutathione metabolism will be implemented into the metabolic network as well. [Pg.82]

Table 17 lists a number of reactions of hydroxide ion and, for comparison, superoxide ion with electron donors. These reactions are classified conventionally and according to the categories shown in Scheme 14. When water is replaced by a dipolar aprotic solvent (e.g. MeCN or DMSO), many of these electron donor-electron acceptor reactions proceed at dramatically faster rates and produce much larger yields of free-radical products. (DMF is generally avoided because of the possible hydrolysis of the amide bond by hydroxide ion). ... [Pg.3489]

Inductive activation of the amide by the adjacent fluorine atom allows for the basic hydrolysis of the amide bond under relatively mild conditions (warming to 75 °C in a biphasic solution of 2 N sodium hydroxide in a 2 2 1 mixture of water, terf-butyl alcohol, and methanol) to form carboxylic acids with high enantiomeric excess (eq 26). ... [Pg.494]

The relative lack of reactivity of the amide bond is notable in proteins, which are polymers of amino acids connected by amide linkages (Section 22.6B). Proteins are stable in aqueous solution in the absence of acid or base, so they can perform their various functions in the aqueous cellular environment without breaking down. The hydrolysis of the amide bonds in proteins requires a variety of specific enzymes. [Pg.857]

Amides are hydrolyzed slowly in comparison to esters. Consequently, hydrolysis of the amide bond of procainamide is relatively slow compared with hydrolysis of the etster linkage in procaine. Drugs in which amide cieavage has been reported to occur, to some extent, include lidocaine. carbainazepine. indomethacin. and prazosin (Mini-... [Pg.110]

Hydrolysis of the amide bond is the best-known reaction of this functional group, in the biological context (digestion of proteins by proteinases) as well as in the organic chemical context (aqueous hydrolysis in 6 M hydrochloric acid for 12 h at 120 °C or by dilute alkali). However, the essential role of a catalyst is made clear by the fact that a peptide dissolved in pure water survives unchanged for many months, even under reflux. [Pg.57]

Other Synthetic Polymeric Filme. Various enzymes have been covalently Immobilized to the surface of synthetic polymer films. For example, the surface of a Nylon film can be activated either by the partial hydrolysis of the amide bonds or by methylation with dimethyl sulfonic acid. Subsequently, an enzyme Is covalently Immobilized to the surface (28). [Pg.450]

A device for retention of a dopamine prodrug into the central nervous system has been designed by the synthesis on N-methyl-dihydronicotinoyl amides of dopamine 3,4-0-diesters, such as 23, which are converted into a quaternary pyridinium derivative by oxidation, and thereby retained inside the blood-brain barrier [19]. Only modest dopamine-like activity was observed, and this may due to a slow rate of enzymatic hydrolysis of the amide bond joining the dopamine and the pyridinium moieties. [Pg.72]


See other pages where Hydrolysis of the Amide Bond is mentioned: [Pg.311]    [Pg.303]    [Pg.134]    [Pg.142]    [Pg.143]    [Pg.264]    [Pg.281]    [Pg.417]    [Pg.303]    [Pg.371]    [Pg.303]    [Pg.355]    [Pg.270]    [Pg.197]    [Pg.686]    [Pg.190]    [Pg.786]    [Pg.1768]    [Pg.41]    [Pg.283]    [Pg.469]    [Pg.303]    [Pg.14]    [Pg.19]   


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Amide bond hydrolysis

Amide bonds

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Amides: , bonding

Bonds hydrolysis

Hydrolysis bonding

Hydrolysis of amides

The Amides

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