Thioether side chains

The thioether side chains of methionine units in proteins can be oxidized with hydrogen peroxide to the corresponding sulfones (Eq. 3-48). They can also be alkylated, e.g., by CH3I to form R—S+(CH3)2. 

Metals ions such as silver or mercury have been coordinated to thioether side chains linked to a polyphosphazene skeleton.109... 

The predicted electronic delocalization onto the thioether side chain in the mtc phenoxyl free radical ground state has been conhrmed experimentally by EPR measurements on mtc specihcally deuterated in the side... 

Galande, A.K., Bramlett, K.S., Burris, T.P., Wittliff, J.L. and Spatola, A.F. (2004) Thioether side chain cydization for helical peptide formation inhibitors of estrogen receptor-coactivator interactions. The Journal of Peptide Research, 63, 297—302. 

The interaction of the thioether side-chain of methionine with the Cp Rh complex appears to be less strong than the interaction of the imidazole side chain of histidine as suggested by the values for Gly-Gly-His and Gly-Gly-Met (entry 7 and 10). Several peptides without His/Met residues were investigated, all of which showed a very low relative binding constant (entries 11-15). It is interesting to note that the substitution of a single His residue with an Ala residue resulted in a drop of affinity of more than five orders of magnitude (entry 1 and 12). 

Goldoni, R, R.A.J. Janssen, and E.W. Meijer. 1999. Synthesis and characterization of new copolymers of thiophene and vinylene Poly(thienylenevinylene)s and poly(terthienylenevinylene)s with thioether side chains. / Polym Sci A 37 4629-4639. 

The combination of sulfur and nitrogen donor atoms in crown ethers appears to provide an ideal binding site for Hg + as several sensors, mainly electrochemical, which use azathiacrown ethers to target the metal have been reported. The selectivity for mercury over other metals is often astonishingly high. " A 15-crown-5 C-pivot lariat ether incorporating a thioether side chain was found to extract 46% of Hg + from aqueous solution into dichloroethane, although it was also able to remove almost 100% of Ag+ under the same conditions. ... 

Fig. 9.37 The synthesis of polythiophenes with thioether side chains.

Scheme 18. The synthesis of regioregular PTs with thioether side chains.

FIGURE 9.19 Proteins containing the C-terminal sequence CAAX can undergo prenylation reactions that place thioether-linked farnesyl or geranylgeranyl groups at the cysteine side chain. Prenylation is accompanied by removal of the AAX peptide and methylation of the carboxyl group of the cysteine residue, which has become the C-terminal residue. 

Much of the current work is based on the fact that the side chain can be replaced by an alternative functionality, which contains sulfur. Metabolic destruction presumably involves the readily oxidized thioether groups. 

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... 

Cysteine sulfhydryls and cystine disulfides may undergo a variety of reactions, including alkylation to form stable thioether derivatives, acylation to form relatively unstable thioesters, and a number of oxidation and reduction processes (Figure 1.10). Derivatization of the side chain sulfhydryl of cysteine is one of the most important reactions of modification and conjugation techniques for proteins. 

Although the primary utility of active halogen compounds is to modify sulfhydryl groups in proteins or other molecules, the reaction is not totally specific. Iodoacetyl (and bromoacetyl) derivatives can react with a number of functional groups within proteins the sulfhydryl group of cysteine, both imidazolyl side chain nitrogens of histidine, the thioether of methionine, and... 

Figure 9.34 The long side chain of this BODIPY derivative contains a sulfhydryl-reactive iodoacetamide group that can couple to a thiol group to form a thioether bond.

Quench the reaction by immediate gel filtration on a desalting column. If a dextran-based resin is used for the chromatography, the support itself will react with sodium periodate to quench excess reagent. Alternatively, N-acetylmethionine may be added to quench the reaction, because the thioether of the methionine side chain will react with periodate to form sulfoxide or sulfone products (Geoghegan and Stroh, 1992). In addition, sodium... 

---