Serine O-sulfate

Beta-chloroalanine and serine O-sulfate can undergo (3 elimination (as in Eq. 14-29) in active sites of glutamate decarboxylase or aspartate aminotransferase. The enzymes then form free aminoacrylate, a reactive molecule that can undergo an aldol-type condensation with the external aldimine to give the following product.1... 

Schnackerz et al. (1979). The same adduct was isolated from glutamate decarboxylase following inactivation with serine O-sulfate (Likos et al., 1982). The mechanism proposed to account for this observation involves elimination of sulfate from the inactivator followed by transimination with the active site lysine of the enzyme (Fig. 9). The released aminoacrylate then rotates in the active site and acts as a nucleophile, attacking the electrophilic imine. Under basic conditions the enzyme lysine is eliminated, generating the free cofactor adduct. This reaction is therefore unusual in that the inactivator is ultimately the nucleophilic partner in the inactivation reaction, in contrast to all of the reactions described to this point, in which the enzyme provides the nucleophile. 

Cyclic sulfamidites and cyclic sulfamidates have been prepared from l-serine. L-Serine was first converted into L-serine-O-sulfate in 40% yield, which was then converted into l,2,3-oxathiazolidine-4-carboxylate 2,2-dioxide (67BCJ1554) in poor yield. Later, Baldwin et al. (90TA881) reported an excellent overall yield of cyclic sulfamidate (52) derived from l-serine (49), as shown in Scheme 10. 

Chloroalanine has been found to be an irreversible inhibitor of the pyridoxal phosphate-linked yS-aspartate decarboxylase/ aspartate aminotransferase/ and alanine racemase. The mechanism of inhibition is shown above by Eq. (7) (the sulfate reacts in the same manner) amino-ethane sulfonate irreversibly inhibits pyridoxal phosphate-linked GABA transaminase and L-serine-O-sulfate irreversibly inhibits aspartate aminotransferase. ... 

Serine protease, 197, 205-216, 220-225 active site, 198 L-Serine-O-sulfate, 37 Sigma ([Pg.772]

To date, the O-sulfation of hydroxyamino acids as residues in proteins or as free amino acids has not been detected. Similarly, desulfation by sulfatases has been observed only for sulfated serine, but it could not be attributed unambiguously to a sulfatase.11301 This lack of natural occurrence explains why only marginal attention has been paid to the synthesis of sulfated hydroxyamino acid peptides. 

This evidence is consistent with, but does not provide definitive proof for OAS being the physiologically important precursor of cysteine. Only a limited number of O-esters of serine have been tested for activity with cysteine synthase (Section II,B,2), and no systematic studies have been made to determine whether serine O-esters other than OAS are synthesized by plants, or to identify the physiologically important a-aminopropionyl donor for cysteine synthesis. Experiments analogous to those used to identify the a-aminobutyryl donor for cystathionine and homocysteine synthesis (Section III,A,3) and the physiological carrier in sulfate reduction in Chlorella (Section IV,D,3) should be informative in this respect. 

Peptides and amino acids may be sulfated the hydroxyl groups of serine and threonine reacted with chlorosulfonic acid in trifluoroacetic acid to give the O-sulfate esters. The free amino groups did not react since they were completely protonated in the strongly acidic media and the rates of sulfonation were determined. Peptides containing the above amino acids were also sulfated. The aromatic amino acids tyrosine and tryptophan, by treatment with chlorosulfonic acid-trifluoroacetic acid, afforded the arylsulfonic acid derivatives. In the solid phase synthesis of cholecystokinin-33, tyrosine has been sulfated to the O-sulfate with chlorosulfonic acid and this was incorporated into the peptide sequence. ... 

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. 

Figure 9.14 Proteoglycan aggregate found in cartilage. C and N are C and N termini of the core protein. Long wavy lines represent chondroitin sulfate, whereas the short lines represent keratan sulfate. All are linkied to the core protein via the O-serine linkage, except for a few oligosaccharide chains near the N terminus of the core protein. LP is link protein, and HA is hyaluronic acid. (Reproduced by permission from Hascall V. Introduction. Functions of the Proteoglycans, Ciba Foundation Symposium 124. New York Wiley Sons, 1986, p. 2.)...

Besides HF and TFA, the two extremes of acid treatment generally employed in the final deprotection step, alternative acids have been proposed, such as MsOH and TfOH, particularly in the context of arginine protection (Table 2). These acids, however, are known to generate serious side reactions such as aspartimide formationt and an N O shift at serine or threonine residues.Moreover, independent of the type of arylsulfonyl group employed, cations originating from the acid-mediated cleavage lead to alkylation and arylsulfonylation of reactive side chains, as present in tryptophan and tyrosine residues. Additionally, sulfation of hydroxy groups is even observed, as well as... 

In most analyzer systems O-phosphoserine and O-phospho-threonine elute at the same volume as cysteic acid (the unretarded position) and can, therefore, interfere with analyses for cysteic acid (and vice versa). The color value for O-phosphoserine is 1.04 times the average value calculated for the amino acids (except proline and cystine) eluted from a 60 cm column in a two-column system (Beckman manuals). It should be noted that O-serine sulfate and O-threonine sulfate, which can be formed during preparation of hydrolysates in the presence of sulfate (Moore 1963 Murray and Milstein 1967), also elute in this position. Electrophoresis at pH 3.5 is an effective means of separating O-phosphoserine from other amino acids, since it migrates... 

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