Enzymatic attack

Mention should also be made here of the extensive use of poly(vinyl alcohol) in potentially biodegradable applications. At appropriate hydroxyl contents these polymers will dissolve in water (see Chapter 14) and can apparently be conveniently washed away after use as a water-soluble packaging. Biodegradation does, however, appear to be slow and first requires an oxidative step involving enzymatic attack to a ketone such as polyenolketone, which then biodegrades more rapidly. 

More definitive evidence of enzymatic attack was obtained with 1 1 copolymers of e-caprolactone and 6-valerolactone crosslinked with varying amounts of a dilactone (98,99). The use of a 1 1 mixture of comonomers suppressed crystallization and, together with the crosslinks, resulted in a low-modulus elastomer. Under in vitro conditions, random hydrolytic chain cleavage, measured by the change in tensile properties, occurred throughout the bulk of the samples at a rate comparable to that experienced by the other polyesters no weight loss was observed. However, when these elastomers were implanted in rabbits, the bulk hydrolytic process was accompanied by very rapid surface erosion. Weight loss was continuous, confined to the... 

While screening for p-lactam antibiotics stable to p-lactamases, a strain of Streptomyces lactamdurans was found to contain several such agents which have a 6-a-methoxy group whose electronic and steric properties protect the antibiotic from enzymatic attack. Cephamycin C (29a), one of these substances, is not of commercial value, but side chain exchange has led to much more potent materials. Of the various ways of effecting this transformation, one of the more direct is to react cephamycin C with nitrous acid so that the aliphatic diazo product (29b) decomposes by secondary amide participation giving cyclic iminoether 30. The imino ether moiety solvolyzes more readily than the p-lactam to produce 7-aminocephamycinic... 

The conversion rates of individual components in a commercial LAS mixture are dependent on the molecular structure. For example, the length of the alkyl chain is positively correlated with the primary degradation rate, and as such, isomers with the phenyl substituted at central positions are degraded more slowly than other isomers [79,80]. Both effects are a direct consequence of the enzymatic attack on the hydrophobic moiety. The relation between surfactant structure and the biodegradation has been termed as Swisher s distance principle which, in summary, describes that an increased distance between... 

In a series of ten morphine 3-benzoates, large differences in rates of enzymatic hydrolysis were seen [122], In 80% human plasma at pH 7.4 and 37°, the unsubstituted 3-benzoate had a tm value of 0.6 h, whereas esters of 2,6-disubstituted benzoic acid were much more resistant to enzymatic attack (t1/2 ranging from 60 h for the dimethylbenzoate to 300 h for the dichloro-and dimethoxybenzoates). Although these results point to marked steric hindrance, electronic effects cannot be excluded but escape characterization because of the limited series. Furthermore, and as mentioned repeatedly in this text, the possibility of binding to plasma proteins is a complicating factor that should be kept in mind. 

Fig. 10.29. Stereochemistry of the EH-catalyzed hydration of 1,2-epoxycyclohexane (10.5) to the chiral tiansfR,R)-cyclohexane-l,2-diol (10.124). The substrate in the catalytic site adopts the conformation shown (3,4M helicity), and enzymatic attack occurs at the (,S )-con figured C-atom with /ra .v-diaxial opening [185][186]. 

Srebotnik, E. and Messner, K. (1990). Enzymatic attack of wood is limited by the inaccessibility of the substrate. In Biotechnology in Pulp and Paper Manufacture, Kirk, T.K. and Chang, H. (Eds.). Butterworth-Heinemann, London, UK, pp. 111-122. 

The aim of this study was to verify previous conclusions that dentin collagen resists enzymatic attack after reaction with glucose. The results show that, following the Maillard reaction, dentin collagen indeed is less degraded by pepsin, but not by trypsin. 

Specific Diffusion-based Limitations to Decay. If microbial colonization is confined to the surface of materials, the decay rate will inevitably be lower than seen where proximity between substrate and microbial cells is possible because enzymes produced by the cell and soluble products formed by enzymatic attack must diffuse a considerable distance. For example, if closer contact between the starch face and fungus were possible than seen in Figure 2, uptake of starch digestion products would occur at the growing tip and translocation within the mycelium by active transport would be possible. This... 

Microbial vulnerability of polymers is often ascribed to enzyme activity, enzymes being crucial players in the biological biodeterioration process. As enzymes are macromolecular polymers, their attack on the polymer is usually only possible via superficially exposed polymer structures readily accessible via a microporous structure. Alternatively, the enzymatic attack works indirectly via... 

As a general mechanism, the degradation of PVA starts outside the cells via enzymatic attack on the polymer. The resulting products are a mixture of acetoxy hydroxy and hydroxy fatty acids. Upon intracellular enzymatic deacetylation, hydroxy fatty acids are generated that can be further metabolised via the classical p-oxidation pathway and TCA cycle. 

Chain degradation proceeds at the oxidised sites, where two different routes can be discerned. One way uses the p-hydroxy ketone functionalities introduced by the initial enzymatic attack as direct substrates in an aldolase-like scission reaction. The other way proceeds via further oxidation of this structure to a 1,3-diketone, which serves as a target structure for a hydrolase-type splitting enzyme. 

The META system (291-293) is an expert system, based on well-established sources, for predicting the sites of potential enzymatic attack and the metabolites formed by metabolic transformations. The program uses dictionaries of biotransformation operators, which are created by experts to represent known metabolic paths. Currently, META can be combined with one of the following dictionaries mammalian metabolism, aerobic biodegradation, anaerobic biodegradation, and metabolic transformation reactions (291). 

Cellulose can be converted to sugar by the following enzymatic attack... 

Large substituents often prevent enzymatic attack on a drug, thereby prolonging its useful life. This technique was used to impart resistance to p-lactamase to the semisynthetic penicillins. The need for the proximity of the phenyl group to the lactam is quite interesting phenylbenzyl penicillin (8-26) is inactive as an enzyme inhibitor because the phenyl group no longer hinders access of the enzyme to the lactam bond. 

The structure of alpha-0 is designed to overcome these two restrictions. A methyl group on the oxygen (the O-methyl) removes the polarity restriction. A methyl group next to the amine function (the alpha-methyl) protects the molecule from enzymatic attack. With the two obstacles removed, this compound apparently has easy access directly to the brain. Hence, alpha,O-dimethylserotonin (a,0-DMS) goes directly into the central nervous system and has proved to be one of the most potent tryptamines yet described. And it is active following oral administration, where it is exposed to all of the body s protective machinery. 

---