Of hydroxy amino acid

On the basis of the close correlation between the number of hydroxy-amino acids in bovine submaxillary mucin and the number of hexosamine and sialic acid residues, Hashimoto and Pigman (34) proposed that an O-glycosidic linkage was the only one that could be present in large amounts. Anderson et al. (38) reported a disappearance of much of the serine after incubation of the proteoglycan of chondroitin sulfate with alkali and suggested that this loss resulted from a -elimination reaction. 

Silyl ethers of hydroxy amino acids have been employed in both solid-phase and solution peptide synthesis. Since the TBDMS and TBDPS ether groups are stable to piperidine and other basic reagents, these derivatives of Ser and Thr (Tables 8 and 9) can be used in the Fmoc strategy.Homodetic peptides and depsipeptides have also been synthesized using TBDMS hydroxy protection for phenyllactic acid and hydroxyisovaleric acid, respectively. 

Analysis of the TBPA-Ti complex (39,40) indicates that the binding site for the hormone is located deep inside the channel. The hormone makes extensive interactions with the protein side chains that project into the channel. The 4 -hydroxyl of Ti interacts with a patch of hydroxy-amino acids of the protein while each of the iodines makes contact with a number of hydro-phobic protein residues. The T amino acid side chain functional groups are in appropriate positions to interact with glutamic acid and lysine residues. Thus, this channel provides a favorable environment for each of the characteristic substituents of the thyroid hormone (40). However, because of the Ti orientation disorder in the protein complex, this structural model is not a sensitive measure of the observed correlations between diphenyl ether conformations and binding affinity data. 

Sakami, W., and G. Toennies The Investigation of Amino Acid Reactions by Methods of Non-aqueous Titrimetry. II. Differential Acetylation of Hydroxy-Groups and a Method for the Preparation of the O-Acetyl Derivatives of Hydroxy Amino Acids. J. biol. Chem. 144, 203 (1942). 

Side-chain halogenated amino acid derivatives are reduced, deuterated, allylated and alkylated with stannanes and related reagents in free-radical processes [53]. Other side-chain functional groups may also be manipulated to produce amino acid radicals [8, 54-58], and, in particular. Barton decarboxylation of aspartate and glutamate derivatives has been applied in this manner (Scheme 8) [55]. Related procedures have been developed to generate amino acid radicals by dehydrox-ylation of hydroxy amino acid derivatives [56]. Hydroxy amino acid derivatives may also be converted to nitrate esters, from which the corresponding alkoxy radi-... 

Scheme 3.2-5 A method that does not require base to form ethers of hydroxy amino acids.

Substitution in the amino or carboxyl group or in both transforms amino acids into acids, bases or neutral compounds, i. e., the zwitter ion character is lost. The derivatives remain more or less polar, depending on the type of substituent. This must be borne in mind when the solvent is chosen. Substitution products which still possess a free carboxyl and free amino group (e. g., monoacyl derivatives of basic amino acids, monoesters of acidic amino acids or ethers of hydroxy-amino acids) behave chromatographically like free amino acids. 

X0 moiety is incorporated in an amino acid, reduction of that group is a common method for the preparation of hydroxy amino acids. There are many methods for the reduction of a ketone moiety to an alcohol. 

In this way, a-ketobutyric acid formed from threonine can yield another amino acid, a-amino-butyric acid, via a transamination reaction. Reaction 1.51 is responsible for losses of hydroxy amino acids during protein hydrolysis. 

The formation of these compounds is based on the following reactions 1,2-elimination in the case of hydroxy amino acids and thio amino acids results in 2-amino-acrylic acid (dehydroalanine) or 2-aminocrotonic acid (dehydro-aminobutyric acid) ... 

Similar to the above mentioned on-resin glycosylation of hydroxy amino acids, the solid-phase elongation of saccharide chains linked to peptides has also been described. With the help of this method the preparation of T antigen carrying MUC2... 

Ecample Miller and Rich investigated the conformational consequences of substitutions on an amino acid in cyclosporin A, an important immunosuppressive drug. One of the amino acids in this cyclic undecapeptide is (2, 3r, 4r, 6e)-3-Hydroxy-4-methyl-2-(methylamino)-6-octenoic acid (MeBmt). It is essential for biological activity. 

Methylmercaptopropionaldehyde is also used to make the methionine hydroxy analog CH2SCH2CH2CH(OH)COOH [583-91 -5] which is used commercially as an effective source of methionine activity (71). AH commercial syntheses of methionine and methionine hydroxy analog are based on the use of acrolein as a raw material. More than 170,000 tons of this amino acid are produced yearly (30) (see Amino acids). One method for the preparation of methionine from acrolein via 3-methyhnercaptopropionaldehyde is as follows. 

A variety of a-amino acid derivatives, including the acids themselves, haUdes, esters, and amides can be transformed iato hydantoias by coadeasatioa with urea (67). a-Hydroxy acids and thek nitriles give a similar reaction (68) ... 

A second, conceptually distinct chiral synthesis of monobactams was developed from P-hydroxy amino acids. As shown in Figure 2, cycli2ation of the acylsulfamate of an amino-protected 0-mesylserine derivative (14, R = H) leads directiy to the monobactam (15). This methodology was also appHed to the synthesis of 4a- (15, R = CH ) and 4P-methyl monobactams from L-threonine and aHothreonine, respectively (17). The... 

Hydroxy-4-methylthiobutyric acid [583-91 -5] the hydroxy analogue of the amino acid methionine, is manufactured by acid hydrolysis of 3-methylthiopropionaldehyde cyanohydrin [17773-41-0] which is produced by the reaction of methyl mercaptan with acrolein (qv). 

FIGURE 5.5 (a) The hydroxy amino acids serine and threonine are slowly destroyed during the course of protein hydrolysis for amino acid composition analysis. Extrapolation of the data back to time zero allows an accurate estimation of the amonnt of these amino acids originally present in the protein sample, (b) Peptide bonds involving hydrophobic amino acid residues snch as valine and isolencine resist hydrolysis by HCl. With time, these amino acids are released and their free concentrations approach a limiting value that can be approximated with reliability. 

The NAD- and NADP-dependent dehydrogenases catalyze at least six different types of reactions simple hydride transfer, deamination of an amino acid to form an a-keto acid, oxidation of /3-hydroxy acids followed by decarboxylation of the /3-keto acid intermediate, oxidation of aldehydes, reduction of isolated double bonds, and the oxidation of carbon-nitrogen bonds (as with dihydrofolate reductase). 

Some workers avoid delay. Pai)adium-on-carbon was used effectively for the reductive amination of ethyl 2-oxo-4-phenyl butanoate with L-alanyl-L-proline in a synthesis of the antihyperlensive, enalapril maleate. SchifTs base formation and reduction were carried out in a single step as Schiff bases of a-amino acids and esters are known to be susceptible to racemization. To a solution of 4,54 g ethyl 2-oxO 4-phenylbutanoate and 1.86 g L-alanyl-L-proline was added 16 g 4A molecular sieve and 1.0 g 10% Pd-on-C The mixture was hydrogenated for 15 hr at room temperature and 40 psig H2. Excess a-keto ester was required as reduction to the a-hydroxy ester was a serious side reaction. The yield was 77% with a diastereomeric ratio of 62 38 (SSS RSS)((55). 

The (5)-enantiomer of this amino acid is available by an analogous procedure starting from (5)-2-hydroxy-l,2,2-triphenylethyl acetate81. 

Racemic a-amino amides and a-hydroxy amides have been hydrolyzed enantio-selectively by amidases. Both L-selective and o-selective amidases are known. For example, a purified L-selective amidase from Ochrobactrum anthropi combines a very broad substrate specificity with a high enantioselectivity on a-hydrogen and a,a-disubstituted a-amino acid amides, a-hydroxyacid amides, and a-N-hydroxya-mino acid amides [102]. A racemase (a-amino-e-caprolactam racemase, EC 5.1.1.15) converts the o-aminopeptidase-catalyzed hydrolysis of a-amino acid amides into a DKR (Figure 6.38) [103]. 

On the other hand, resonance assignments for CP of threonine and serine, and C and Cy of hydroxy proline, were difficult to make, because of their proximity to carbohydrate carbon resonances. In most cases then, the resonances were assigned on the basis of the effects of pH on the chemical shifts of those resonances. It was shown that the chemical shifts for the carbohydrate carbon resonances were virtually unaffected (AS 0.4 p.p.m.) when going from the cationic state (pH 2) to the anionic state (pH 11) of the amino acid residues. The chemical shifts of C and CP of the amino acid residues, however, shifted considerably (up to 3.1 and 6.6 p.p.m. for C" and CP, respectively see Table VI). 

As mentioned in the Introduction, a variety of unusual carbohydrate -protein linkages is found in Nature. These may be placed in several categories (i) carbohydrates O-glycosylated to jff-hydroxy amino acids (ii) carbohydrates S-glycosylated to cysteine (Hi) carbohydrates N-gly-cosylated to the N-terminal amino group of the protein or (iv) in some... 

These substances include primarily depsipeptides (compounds whose structural units consist of alternating amino acid and ar-hydroxy acid units). Their best-known representative is the cyclic antibiotic, valinomycin, with a 36-membered ring [L-Lac-L-Val-D-Hy-i-Valac-D-Val]3, which was isolated from a culture of the microorganism, Streptomyces fulvissimus. Figure 6.13 depicts the structure of free valinomycin and its complex with a potassium ion, the most important of the coordination compounds of valinomycin. 

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