Thioether amino acids

Scheme 1 The Structures of the Naturally Occurring Thioether Amino Acids meso-Lanthionine and threo-Methyllanthionine and Common Abbreviations within the Peptide Chain, Alanine and Threonine Denote the Amino Acid Core Structures Linked to the Sulfur Atom through the Side Chain...

One problem of prime importance is the reliable determination of the number of residues of ,/3-unsaturated amino acids in proteins. Direct amino acid analysis subsequent to total hydrolysis of proteins is not feasible. The ,/3-unsaturated amino acids are subject to degradation with the formation of amide (ammonia) and -keto-acid. The numbers and types of ,/3-unsaturated amino acids in nisin (1) and subtilin (10) and in the fragments of the two peptides were, nevertheless, determined by amino acid analysis, only, however, after the addition of mercaptan across the double bonds of dehydroalanine and dehydrobutyrine (19). Using benzylmercaptan, the addition products are S-benzylcysteine (from dehydroalanine) and /3-methyl-S-benzylcysteine (from dehydrobutyrine). The two thioether amino acids are eluted from ion exchange columns of the amino acid analyzer free from interference by other amino acids... 

Dehydroalanine (Dha) and dehydro-a-aminobutyric acid, a putative dehydration product of threonine occur accumulated in a particular class of antibiotic fungal peptides recently named lantibiotics of which Nisin (Fig. 26) will be mentioned first. The structure of the 34-peptide as revealed by Erhard Gross and coworkers in the beginning of the seventies, contains three dehydro side chains, RCH=C(NH—)CO—, and five thioether amino acids, lanthionine, Ala-S-Ala and its homolog Abu-S-Ala. Total synthesis by the group of Tetsuo Shiba (Plate 43) [61]. 

Epstein, W. W., D. C. Lever, and H. C. Rilling, Prenylated proteins Synthesis of geranylgeranylcysteine and identification of this thioether amino acid as a component of proteins in CHO cells, Proc. Natl. Acad. Sci. USA, 87, 7352-7354 (1990). 

Gross, E., and S. Matsuura a,P-Unsaturated and Thioether Amino Acids in Peptide Synthesis. In Peptides, Chemistry, Structure and Biology Proceedings of the 4th American Peptide Symp. 1975, p. 351. 

In aqueous solutions at pH 7, there is little evidence of complex formation between [MesSnflV)] and Gly. Potentiometric determination of the formation constants for L-Cys, DL-Ala, and L-His with the same cation indicates that L-Cys binds more strongly than other two amino acids (pKi ca. 10,6, or 5, respectively). Equilibrium and spectroscopic studies on L-Cys and its derivatives (S-methyl-cystein (S-Me-Cys), N-Ac-Cys) and the [Et2Sn(IV)] system showed that these ligands coordinate the metal ion via carboxylic O and the thiolic 5 donor atoms in acidic media. In the case of S-Me-Cys, the formation of a protonated complex MLH was also detected, due to the stabilizing effect of additional thioether coordination. ... 

Thiols, thioethers and sulfoxides [37-39] e.g. sulfur-containing amino acids... 

In addition to the backbone donor system the amino acid residues can contain a variety of donor centers (679E). The most important of these are the imidazole N atoms of His, the S atom of Cys, and to some extent the, 3-carboxylate O atom of Asp. Other side chain donors like the O atoms of Ser and phenolic O atoms of Tyr or amino N atoms of Lys are of minor importance for coordination of Ni11 ions. Also, thioether S-donors of Met play only a minor role in the interactions with Ni11 ions.1730... 

The iodoacetyl group of both isomers reacts with sulfhydryls under slightly alkaline conditions to yield stable thioether linkages (Figure 9.7). They do not react with unreduced disulfides in cystine residues or with oxidized glutathione (Gorman et al., 1987). The thioether bonds will be hydrolyzed under conditions necessary for complete protein hydrolysis prior to amino acid analysis. 

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