Enzyme resistance

Berman JM, Goodman M, Nguyen TM-D, Schiller PW. Cyclic and acyclic partial retro-inverso enkephalins mu receptor selective enzyme resistant analogs. Biochem Biophys Res Commun 1983 115 864-870. 

The enzyme-resistant residue left after ribonuclease action is not dialyz-able and was believed to have a high molecular weight. This has now been shown to be due not to molecular size but to electrostatic effects, and in the presence of salts the enzyme-resistant core readily dialyzes.212 Moreover, it consists of a mixture of relatively small oligonucleotides containing some di- and tri-nucleotides.96 Some of these oligonucleotides have been charac-... 

Cellosize Enzyme, Resistant Hydroxyethyl Cellulose, 1984 Product Bulletin, Union Carbide Corp., Old Ridgebury Road, Danbury, CT 06817. 

Oxidant production (e.g., dihydroethidium, dichlorofluor-escein), antioxidant changes (e.g., glutathione = mono-chlorobimane), antioxidant system enzyme, resistance to dye oxidation (e.g., total antioxidant status), macromolec-ular oxidation byproducts (e.g., malondialdehyde, hydro-xynonenal, 8-hydroxyguanosine)... 

Efforts to overcome the actions of the p-lactamases have led to the development of such p-lactamase inhibitors as clavulanic acid, sulbactam, and tazobactam. They are called suicide inhibitors because they permanently bind when they inactivate p-lactamases. Among the p-lactamase inhibitors, only clavulanic acid is available for oral use. Chemical inhibition of p-lactamases, however, is not a permanent solution to antibiotic resistance, since some p-lactamases are resistant to clavulanic acid, tazobactam, or sulbactam. Enzymes resistant to clavulanic acid include the cephalosporinases produced by Citrobacter spp., Enterobacter spp., and Pseudomonas aeruginosa. 

Vidarabine s specific mechanism of action is not fully understood. Cellular enzymes convert this drug to a triphosphate that inhibits DNA polymerase activity. Vidarabine triphosphate competes with deoxyadeno-sine triphosphate (dATP) for access to DNA polymerase and also acts as a chain terminator. Although vidarabine is incorporated into host DNA to some extent, viral DNA polymerase is much more susceptible to inhibition by vidarabine. Vidarabine also inhibits ri-bonucleoside reductase and other enzymes. Resistance occurs as a result of DNA polymerase mutation. 

It is more difficult to prepare a chiral a,a-dialkylammo acid. Nevertheless, when such analogues are incorporated into the backbone of a peptide chain, analogues with modified properties are obtained. In this context, such residues have been evaluated as a new type of conformational constraint for the synthesis of enzyme-resistant agonists and antagonists of bioactive peptides. Here, the asymmetric synthesis or the resolution of the chiral quaternary amino acid is necessary and numerous procedures, which have recently been reviewed, were developed to produce the requisite amino acids in enantiomerically pure form. 

Steeping and wet-milling processes are also utilized to separate soluble compounds from com. One process involves removal of soluble starch and protein from com by steeping com in a warm sulfurous acid solution for about one to two days. The undissolved com solids are then coarsely wet-milled and processed to collect the oil-containing germ for com oil production. Also, for more enzyme-resistant cellulose biomass, sulfuric acid or hydrochloric acid can be used to digest the cellulose polysaccharide into fermentable molecules. 

Modifications designed to enhance the enzyme resistance and prolong the activity of SS derivatives have been quite successful. The use of D-amino acids instead of the normal L-enantiomers (e.g., in Trp ), or replacement of the disulfide link by a nonreducible ethylene bridge, leads to an increased duration of activity, approaching 3 hours. Several analogs show a greatly increased effect, like the [D-Ala, D-Trp ]somatostatin, which has 20 times the activity of SS on growth hormone release. The NH-terminal outside the cyclic dodecapeptide is not essential for activity. Selectivity of action results from... 

Degradative enzymes Resistance of mucosal barrier Membrane transporters Metabolism at mucosa pH changes Disease conditions... 

Although the majority of the lipids in M. laidlawii membranes appear to be in a liquid-crystalline state, the system possesses the same physical properties that many other membranes possess. The ORD is that of a red-shifted a-helix high resolution NMR does not show obvious absorption by hydrocarbon protons, and infrared spectroscopy shows no ft structure. Like erythrocyte ghosts, treatment with pronase leaves an enzyme-resistant core containing about 20% of the protein of the intact membrane (56). This residual core retains the membrane lipid and appears membranous in the electron microscope (56). Like many others, M. laidlawii membranes are solubilized by detergents and can be reconstituted by removal of detergent. Apparently all of these properties can be consistent with a structure in which the lipids are predominantly in the bilayer conformation. The spectroscopic data are therefore insufficient to reject the concept of a phospholipid bilayer structure or to... 

The formal replacement of the amide by the -CH2—S- group to produce a methylenethio surrogate was one of the first applications of amide bond replacements designed for enzyme inhibition12 and later as enzyme-resistant peptide analogues. 35 ... 

Bjorck, 1., Nyman, M., Pedersen, B., Siljestrom, M Asp, N.G., and Eggum, B.0.1987. Formation of enzyme resistant starch during autoclaving of wheat starch Studies in vitro and in vivo. J. Cereal Sci. 6 159-172. 

Sieved, D. and Pomeranz, Y. 1989. Enzyme-resistant starch. I. Characterization and evaluation by enzymatic, thermoanalytical, and microscopic methods. Cereal Chem. 66 342-347. 

Sieved, D Czuchajowska, Z., and Pomeranz, Y. 1991. Enzyme-resistant starch. III. X-ray diffraction of autoclaved amylomaize Vll starch and enzyme resistant starch residues. Cereal Chem. 68 86-93. 

Enzyme-resistant starch is the subject of the work published by Roopa and Premavalli (2008). 

Englyst et al.248 classified starch into three types RSI, RS2 and RS3. RSI is a starch protected from digestion in the small intestine by a food matrix, such as the intact endosperm of a wheat kernel. RS2 is simply unswollen granular starch. RS3 is starch that was gelatinized, but then retrograded to become enzyme-resistant. Chemically modified (e.g. crosslinked) starch (RS4) has been added to the list.242 The four forms of resistant starch and their measurement are described by Nugent246 and Sajilata et al.249... 

Chloramphenicol (9) is liable to breakdown by chloramphenicol acetyl-transferases [185]. Fluoro derivatives (57, 58) resist enzymatic attack but little has been heard of these, apparently because of their toxicity [319], Aminoglycoside antibiotics (AGACs) may be chemically modified by AMEs. Some derivatives (e.g. amikacin, 43) are more recalcitrant than others, e.g. kanamycin (42) (see Figure 4.2). Other enzyme-resistant AGACs of low toxicity are needed. 

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