Ester-and amide-linked

Papain is a proteolytic enzyme that exhibits a proteolytic activity toward various ester and amide links, as they occur in proteins or peptides. Its performance has been tested with ultrafiltration experiments of casein solutions. The modified membranes show a self-cleaning effect. Whereas the nonenzymatic membranes are completely blocked during ultrafiltration, the enzyme-functionalized membranes do not clog. 

In this section we turn to a consideration of the experimental side of condensation kinetics. The kind of ab links which have been most extensively studied are ester and amide groups, although numerous additional systems could also be cited. In many of these the carbonyl group is present and is believed to play an important role in stabilizing the actual chemical transition state involved in the reactions. The situation can be represented by the following schematic reaction ... 

Ch1orocarhony1trime11itic acid 1,2-anhydride [1204-28-0] (9), is used in the preparation of esters and amide—imide polymers. TriaHyl trimellitate [2694-54-4] (10) is used as a cross-linking or co-curing agent for ethylene-derived mbbers and plastics. 

Methylpyrazole has been investigated as a possible treatment for alcoholism. The stmcture—activity relationship (SAR) associated with a series of pyrazoles has been examined ia a 1992 study (51). These compounds were designed as nonprostanoid prostacyclin mimetics to inhibit human platelet aggregation. In this study, 3,4,5-triphenylpyrazole was linked to a number of alkanoic acids, esters, and amides. From the many compounds synthesized, triphenyl-IJT-pyrazole-l-nonanoic acid (80) was found to be the most efficacious candidate (IC g = 0.4 //M). 

Additional BHT-derived 5-LO inhibitors bear heteroatom-linked 4-substituents. Searle s SC-45662 (50) was selective (25 1) for 5-LO over CO in cRBL (3.7 /iM) and in A23187-stimulated RBL-1 cells (7.1 yuM) [146]. Besides NSAID-like activity in RAA (down to 10 mg/kg p.o.), SC-45662 also inhibited GPB (ED30 16.7 mg/kg p.o.), and LTB4 release from ulcerative colitis rectal mucosal biopsy samples was decreased [147]. Several patents have described similar compounds where the alkyl substituent on sulphur is varied quite widely [148 151]. Oxidation of the distal sulphur was consistent with activity, while replacement of this sulphur with oxygen gave reduced potency. Simple alkyl groups, alkylene-linked esters and amides, and disulphide-linked alkanoic esters were also active in cRBL with similar potency free carboxylic acids were somewhat less potent. Oxidation of the sulphur attached to the phenolic ring destroyed the activity. 

Carboxylic acid derivatives are compounds that possess an acyl group (R—C=0) linked to an electronegative atom, e.g. —Cl, —CO2 R, —OR or —NH2. They can be converted to carboxylic acids via simple acidic or basic hydrolysis. The important acid derivatives are acid chlorides, acid anhydrides, esters and amides. Usually nitriles are also considered as carboxylic acid derivatives. Although nitriles are not directly carboxylic acid derivatives, they are conveniently hydrolysed to carboxylic acids by acid or base catalysts. Moreover, nitriles can be easily prepared through dehydration of amides, which are carboxylic acid derivatives. 

Bodor and Brewster (1983) first used the term CDS, in describing the use of dihydropyridine ester- (or amide)-linked prodrugs such as 27 (X-OH is the parent) which can partition readily into the CNS, there to be oxidized to pyridinium salts (28), which are effectively trapped in the biophase because of their extreme polarity, and which then undergo enzymic or chemical hydrolysis of the now very labile ester link to release active drug. 

A similar distribution of fatty acids has also been detected in lipid A of other bacteria (Fig. 5). Thus, in Fusobacterium nucleatum, 2 moles of (R)-3-OH-14 0 are ester-bound, one of which is 3-O-acylated by 14 0. In amide linkage, (R)-3-0(14 0)-16 0 is present. In Vibrio cholerae, a dimer of (R)-3-OH-12 0 is bound as an ester while (R)-3-0-(14 0)-14 0 and (R)-3-0-(16 0)-14 0 are amide-linked. The lipid A component of Chromobacterium violaceum possesses 2 moles of (R)-3-OH-10 0 in ester linkage. The amide-bound acyl groups are represented by (R)-3-0H-12 0 residues which are 3-0-acylated by 12 0 and (S)-2-OH-12 0. In P. mirabilis, 3-0H-14 0 is, like in Salmonella, ester-and amide-bound. In this case, however, exclusively 14 0 substitutes the 3-hydroxyl groups of both 0- and N-linked 3-OH-14 0. 

Quantitative data on the amounts of free IAA, ester IAA and amide linked IAA have been supplied by Ms. A. Schulze (33). Her data, shown in Table I, permit several conclusions first, all plants examined contain greater amounts of IAA conjugates than free IAA secondly, the cereals contain mainly ester IAA and, thirdly, legumes contain mainly amide linked IAA. 

Comparison of the Structural Units of Ester and Amide. The effect of hydrogen bridges in polyamides has already been mentioned. For a more accurate demonstration of the influence of NH bridges, it would be necessary to compare polyamides with analogous high molecular weight ketones, which have a —CH2 unit instead of the NH chain link (Table VI). Such products are not yet described. Therefore, we have chosen the polyesters for comparison. These have an oxygen chain link instead of the NH chain link. 

Valinomycin is a cyclic structure containing three molecules of L-valine, three molecules of D-valine, three molecules of L-lactic acid, and three molecules of D-hydroxyisovalerate. These four components are linked in an ordered fashion such that there is an alternating sequence of ester and amide Unking bonds around the cyclic structure. This is achieved by the presence of a lactic or hydroxyvaleric acid unit between each of the six vahne units. Further ordering can be observed by noting that the L and D portions of valine alternate around the cycle, as do the lactate and hydroxyisovalerate units. 

Saccharolipidsm, where fatty acids are linked in ester and amide linkages directly to sugar molecules. This is a relatively small class of molecules, best described in bacteria and plants. The most well known of these are the acylated glucosamine precursors of the lipid A component of the endotoxin thought to be responsible for the toxicity of Gram-negative bacteria. A simple monosaccharide precursor. Lipid X, is shown in Table 3.1. 

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