Lysine reaction with

N -Protection of lysine. Reaction with the copper chelate of lysine furnishes the derivative quantitatively. The method is suitable for large-scale preparation. 

Lisinopril can be prepared [29] from the triiiuoroacetamide derivative of lysine. Reaction with phosgene gives the N-carboxyanhydride which reacts with proline. Reductive condensation of the amine is followed by hydrolysis of the triliuoracetamide protective group to give lisinopril. 

Reaction with Phosgene. This reaction of amino acid esters is used for preparing the corresponding isocyanates, especially lysine diisocyanate [4460-02-0] (LDI). LDI is a valuable nonyellowing isocyanate with a functional side group for incorporation in polyurethanes. 

Isocyanate. Lysine has two amino groups in the molecule and dHsocyanate is prepared by reaction with phosgene. Lysine trHsocyanate [69878-18-8] (LTI) is developing on a commercial scale in Japan (244). 

Sundower Seed. Compared to the FAO/WHO/UNU recommendations for essential amino acids, sunflower proteins are low in lysine, leucine, and threonine for 2 to 5-year-olds but meet all the requirements for adults (see Table 3). There are no principal antinutritional factors known to exist in raw sunflower seed (35). However, moist heat treatment increases the growth rate of rats, thereby suggesting the presence of heat-sensitive material responsible for growth inhibitions in raw meal (72). Oxidation of chlorogenic acid may involve reaction with the S-amino group of lysine, thus further reducing the amount of available lysine. 

Heterocyclic enamines A -pyrroline and A -piperideine are the precursors of compounds containing the pyrrolidine or piperidine rings in the molecule. Such compounds and their N-methylated analogs are believed to originate from arginine and lysine (291) by metabolic conversion. Under cellular conditions the proper reaction with an active methylene compound proceeds via an aldehyde ammonia, which is in equilibrium with other possible tautomeric forms. It is necessary to admit the involvement of the corresponding a-ketoacid (12,292) instead of an enamine. The a-ketoacid constitutes an intermediate state in the degradation of an amino acid to an aldehyde. a-Ketoacids or suitably substituted aromatic compounds may function as components in active methylene reactions (Scheme 17). 

Similarly, the rate of inhibition of phosphoenzyme formation by diethylpyrocarbonate (DEPC) was much slower than the loss of ATPase activity [368], Even when the reaction approached completion with more than 90% inhibition of ATP hydrolysis, about 70% of the Ca -ATPase could still be phosphorylated by ATP (2.3nmoles of E P/mg protein). The remaining 30% of E P formation and the corresponding ATPase activity was not reactivated by hydroxylamine treatment, suggesting some side reaction with other amino acids, presumably lysine. When the reaction of the DEPC-modified ATPase with P-ATP was quenched by histidine buffer (pH 7.8) the P-phosphoenzyme was found to be exceptionally stable under the same conditions where the phosphoenzyme formed by the native ATPase underwent rapid hydrolysis [368]. The nearly normal phosphorylation of the DEPC-trea-ted enzyme by P-ATP implies that the ATP binding site is not affected by the modification, and the inhibition of ATPase activity is due to inhibition of the hydrolysis of the phosphoenzyme intermediate [368]. This is in contrast to an earlier report by Tenu et al. [367], that attributed the inhibition of ATPase activity by... 

Yoshioka T, JA Krauser, FP Guengerich (2002) Tetrachloroethylene oxide hydrolytic products and reactions with phosphate and lysine. Chem Res Toxicol 15 1096-1105. 

Interestingly, the nucleophilic addition of water in the sequence of events giving rise to 41 represents a relevant model system for investigating the mechanism of the generation of DNA-protein cross-links under radical-mediated oxidative conditions [80, 81]. Thus, it was shown that lysine tethered to dGuo via the 5 -hydroxyl group is able to participate in an intramolecular cyclization reaction with the purine base at C-8, subsequent to one electron oxidation [81]. 

These initial findings do not exclude other possible formaldehyde-induced reactions with tissue proteins. Notably, this first model system was not designed to detect the role of lysine residues. Lysine has a propensity to react with and form a variety of different types of cross-links with other amino acids in the presence of formaldehyde.1,3 417 Therefore, it is likely to also be important in reactions with formaldehyde. In fact, peptides with internal lysine residues were purposefully excluded from this initial study for technical reasons. To explore the importance of lysine residues in antigen retrieval, an alternative method was employed. 

Formaldehyde reacts with proteins to form adducts and cross-links.31516 Metz et al.3 have identified three types of chemical modifications after treatment of proteins with formaldehyde (a) methylol (hydroxymethyl) adducts, (b) Schiff bases, and (c) methylene bridges. The reaction of formaldehyde with proteins is summarized in Figure 19.1, but briefly, formaldehyde reacts primarily with lysine and cysteine to form methylol adducts. The methylol adduct can subsequently undergo a dehydration reaction to form a Schiff base. Adducted primary amine and thiol groups can undergo a second reaction with arginine,... 

The N-terminal methionine residue of protein can also be employed for selective PEGylation using aldehyde-terminated PEG via a reductive amination reaction, because the N-terminal primary amine has a lower pAa of 7.8 than other amines such as lysines, whose pZa is 10.1 [7]. After reaction with aldehyde-terminated PEG at low pH, the resultant imine is reduced with sodium cyanoborohydrate to provide PEGylated protein (Fig. 4) [8, 9]. This technique was used for the production of Neulasta, which was approved for use by the FDA in 2002 [10]. 

Figure 1.18 Reaction of proline, arginine, and lysine residues with hydroxyl radical results in oxidation of side-chain structures that form carbonyls. Both arginine and proline oxidation result in the same product.

Figure 4.33 Benzidine can be diazotized with sodium nitrite and HC1 for reaction with proteins through their tyrosine, histidine, or lysine side-chain groups.

A sulfonyl chloride group rapidly reacts with amines in the pH range of 9-10 to form stable sulfonamide bonds. Under these conditions, it also may react with tyrosine —OH groups, aliphatic alcohols, thiols, and histidine side chains. Conjugates of sulfonyl chlorides with sulf-hydryls and imidazole rings are unstable, while esters formed with alcohols are subject to nucleophilic displacement (Nillson and Mosbach, 1984 Scouten and Van der Tweel, 1984). The only stable derivative with proteins therefore is the sulfonamide, formed by reaction with e-lysine... 

Reaction with Cr(III) Modified Plastocyanin. From thermo-lysin proteolysis experiments Farver and Pecht (20) have concluded that reduction of PCu(II) with labelled Cr0 20)52+ (1 1 mole amounts) at pH 7 gives a product in which Cr(III) is attached to the peptide chain 40-49. Coordination of the Cr at one or two carboxylates in the 42-45 patch is favoured. It has now been demonstrated that rate constants (25oC) for the reaction of PCu(I).Cr(III) + Co(phen)33+ are decreased by 16%. 

Reaction with Chemically Modified Cytochrome c. Chemically modified (CDNP) cytochrome c derivatives have been prepared by Margoliash and colleagues (22). Lysine residues react as in (17),... 

ROS can modify amino acid side chains, with histidine, tryptophan, cysteine, proline, arginine, and lysine among those most susceptible to attack (Brown and Kelly 1994). As a result, carbonyl groups are generated, and these carbonyl concentrations can be measured directly in plasma by using atomic absorption spectroscopy, fluorescence spectroscopy, or HPLC following reaction with 2,4-dinitrophenylhydrazine. 

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