Racemization protein

Nutritional Implications. The nutritive quality of any protein depends on three factors amino acid composition, digestibility, and utilization of the released amino acids. Bacemization brought about by processing can impair the nutritive value of proteins by (a) generating non-metabolizable forms of amino acids (D-enanticmers), (b) creating peptide bonds inaccessible to proteolytic enzymes, and (c) toxic action (or interaction) of specific D-enanticmers. Little is known concerning the health consequences of human consumption of racemized proteins. No study has specifically evaluated amino acid losses due to racemization within food proteins. 

Dakin, H. D. and Dudley, H. W. (1913). The action of enzymes on racemized proteins and their fate in the animal body. J. Biol. Chan. 15, 271-276. 

Processes for production of ethanol and acetone-butanol-ethanol mixture from fermentation products in membrane contactor devices were presented in Refs. [88,89]. Recovery of butanol from fermentation was reported in Ref. [90]. Use of composite membrane in a membrane reactor to separate and recover valuable biotechnology products was discussed in Refs. [91,92]. A case study on using membrane contactor modules to extract small molecular weight compounds of interest to pharmaceutical industry was shown in Ref. [93]. Extraction of protein and separation of racemic protein mixtures were discussed in Refs. [94,95]. Extractions of ethanol and lactic acid by membrane solvent extraction are reported in Refs. [96,97]. A membrane-based solvent extraction and stripping process was discussed in Ref. [98] for recovery of Phenylalanine. Extraction of aroma compounds from aqueous feed solutions into sunflower oil was investigated in Ref. [99]. 

Pentelute BL, Mandal K, Gates ZP, Sawaya MR, Yeates TO, Kent SBH (2010) Total chemical synthesis and X-ray structure of kaliotoxin by racemic protein crystallography. Chem Commun 46 8174—8176... 

Recent studies have shown that in addition to the structure of the amino acyl residue, the position of the residue in the peptide (or protein) can have a major effect on racemization (69). Therefore, at the end of an exposure to alkali, and depending on the severity of the treatment, a mixture of the original protein and several D-amino acyl residue-containing proteins is likely to result. The latter are not necessarily Identical, i.e., the D-amlno acyl residues may be located at different positions along the primary structure of the protein, thereby giving rise to a heterogenous mixture of racemized proteins. 

Keywords Drug discovery Mirror image phage-display Native chemical ligation Peptide desulfurization Peptide ligation Peptide synthesis Protein chemical synthesis Protein pharmaceutical Racemic protein crystallography... 

Figure 3.1 Gas chromatographic resolution of enantiomers of racemic protein amino acids as their A -pentafluoropropanoyl isopropyl esters on (4). (Boyer, E. Frank, H. In Modification of Polymers Carraher, Jr., C. E. ACS Symposium Series 121 American Chemical Society Washington, DC, 1980 p. 66.)...

It is important to notice that the united-atom simplification cannot be applied to functional hydrogens which are involved in the formation of a hydrogen hond or a salt bridge. This would destroy interactions important for the structural integrity of the protein. Removing the hydrogen at the u-carbon of the peptide backbone is also dangerous, because it prevents racemization of the amino acid. 

A novel technique for dating archaeological samples called ammo acid racemiza tion (AAR) IS based on the stereochemistry of ammo acids Over time the configuration at the a carbon atom of a protein s ammo acids is lost m a reaction that follows first order kinetics When the a carbon is the only chirality center this process corresponds to racemization For an ammo acid with two chirality centers changing the configuration of the a carbon from L to D gives a diastereomer In the case of isoleucme for example the diastereomer is an ammo acid not normally present m proteins called alloisoleucme... 

Although most anesthetics are achiral or are adininistered as racemic mixture, the anesthetic actions are stereoselective. This property can define a specific, rather than a nonspecific, site of action. Stereoselectivity is observed for such barbiturates as thiopental, pentobarbital, and secobarbital. The (3)-enantiomer is modestly more potent (56,57). Additionally, the volatile anesthetic isoflurane also shows stereoselectivity. The (3)-enantiomer is the more active (58). Further evidence that proteins might serve as appropriate targets for general anesthetics come from observations that anesthetics inhibit the activity of the enzyme luciferase. The potencies parallel the anesthetic activities closely (59,60). 

Disopyr mide. Disopyramide phosphate, a phenylacetamide analogue, is a racemic mixture. The dmg can be adininistered po or iv and is useful in the treatment of ventricular and supraventricular arrhythmias (1,2). After po administration, absorption is rapid and nearly complete (83%). Binding to plasma protein is concentration-dependent (35—95%), but at therapeutic concentrations of 2—4 lg/mL, about 50% is protein-bound. Peak plasma concentrations are achieved in 0.5—3 h. The dmg is metabolized in the fiver to a mono-AJ-dealkylated product that has antiarrhythmic activity. The elimination half-life of the dmg is 4—10 h. About 80% of the dose is excreted by the kidneys, 50% is unchanged and 50% as metabolites 15% is excreted into the bile (1,2). 

Brefeldin A, an antiviral agent which impedes protein transport from the endoplasmic reticulum to the Golgi complex, was synthesized as the racemate using a number of interesting diastereoselective reactions. 

The synthesis of an a-amino acid from an achiral precursor by any of the methods described in the previous section yields a racemic mixture, with equal amounts of S and R enantiomers. To use an amino acid in the laboratory synthesis of a naturally occurring protein, however, the pure S enantiomer must be obtained. 

The racemization of the phosphine (118) has been followed by optical rotation. The lack of a solvent effect indicates that there is little change in dipole moment in the formation of the planar transition state. Circular dichroism has been used to study the interactions of nucleotides with proteins and DNA with a histone. Faraday effects have been reviewed. Refraction studies on chloro-amino-phosphines, fluoro-amino-phosphines, and some chalcogenides are reported. 

Capillary electrophoresis employing chiral selectors has been shown to be a useful analytical method to separate enantiomers. Conventionally, instrumental chiral separations have been achieved by gas chromatography and by high performance liquid chromatography.127 In recent years, there has been considerable activity in the separation and characterization of racemic pharmaceuticals by high performance capillary electrophoresis, with particular interest paid to using this technique in modem pharmaceutical analytical laboratories.128 130 The most frequently used chiral selectors in CE are cyclodextrins, crown ethers, chiral surfactants, bile acids, and protein-filled... 

Disruption of the native structure of a protein can also contribute to chemical instability by accelerating the rates of a variety of degradation routes, including deamidation, hydrolysis, oxidation, disulfide exchange, /1-elimination, and racemization. 

Racemization of the native L-amino acid in peptides and proteins to the D-enantiomer generally results... 

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