Protecting groups sulfhydryl

Although a sulfhydryl group generally is not converted to an S-phenyl thioether, thiophenol can be used to introduce sulfur into molecules, and thus the phenyl group serves as a suitable protective group that can be removed by electrolysis (-2.7 V, DMF, R4N+X ). ... 

SAMSA-fluorescein, 5- [2(and 3)-5-(acetylmercapto)-succinoyl]amino fluorescein, is a fluorescent probe containing a protected sulfhydryl group. In its protected state, the compound is unre-active. The acetyl-protecting group can be removed by treatment with dilute NaOH at pH 10.0 (Figure 9.9). The resulting free sulfhydryl derivative can be used to label thiol-reactive crosslinkers or to couple with sulfhydryl residues on proteins and other molecules. After activating... 

Oligonucleotides containing amine groups introduced by enzymatic or chemical means may be modified with SATA (Chapter 1, Section 4.1) to produce protected sulfhydryl derivatives. The NHS ester end of SATA reacts with a primary amine to form a stable amide bond. After modification, the acetyl protecting group can be removed as needed by treatment with hydroxylamine under mildly alkaline conditions (Fig. 401). The result is terminal sulfhydryl groups that can be used for subsequent labeling with thiol-reactive probes or activated-enzyme derivatives (Kumar and Malhotra, 1992). 

Thiol esters are reduced at less negative potentials than carboxylic esters and can be cleaved in protic (e.g., methanol) [141] or aprotic [123, 142] media. Aroyl and benzylox-ycarbonyl groups may thus be used for protection of sulfhydryl groups in MeCN the radical anion of an arylthioic 5 -ester is usually cleaved to alkylthiolate and aryl radical if it is relatively stable (minutes) it reacts eventually with oxygen with formation of an arylcarboxylate [43]. 

The reagent has been used also for protection of the sulfhydryl group of cysteine. The protective group is removed almost quantitatively by treatment with excess sodium methoxide under nitrogen for 5-10 min. at room temperature. 

The t-butyl group is useful also for the protection of the hydroxyl group of serine or tyrosine. The ethers are cleaved by HBr-AcOH or by HCI-CHCI3. The group is not useful for protection of sulfhydryl groups because drastic conditions are required for cleavage. 

Fig. 2. Important reactions involved in the generation of thiol-maleimide links. All of these reactions proceed under neutral conditions. (A) Free sulfhydryl groups undergo additional reactions with maleimide groups. (B) Thioacetate protection groups may be hydrolyzed with hydroxylamine. (C) 2-Pyridyldisulfide protecting groups are reduced by DTT.

The sulfhydryl functional group of Cys is an excellent nucleophile and is easily acylated or alkylated hence it must be protected during SPPS. Oxidation to form the disulfide may also occur if Cys is left unprotected. Many of the suggested protecting groups are compatible with both Boc and Fmoc SPPS as they are not base or acid labile. 

As previously mentioned, Cys is susceptible to a number of side reactions that should be considered before a synthesis. Peptides that have a C-terminal Cys can undergo elimination of the sulfhydryl protected side chain in both Boc and Fmoc SPPS [96,97]. In the latter case 3-(l-piperidi-nyl)alanine is known to form [97]. This has been noted for Cys(Bzl) in Boc SPPS [96] as well as Cys(Acm) and Cys(Trt) in Fmoc SPPS and is dependent on the solid support, the linker, and the side-chain protecting group... 

Protection of sulfhydryl groups as ethyl disulfides Removal of protective groups s. 24,45... 

This special sulfhydryl protecting group can be introduced via the reaction of an S-trityl derivative with methoxycarbonylsulfenyl chloride... 

DithiothreitoljN-methylmorpholine Protection of sulfhydryl groups as S-(N-methyl-N-phenylcarbamyl)disulfides Removal of the protective group under mild conditions... 

Protection of sulfhydryl groups as trityl and diphenylmethyl thioethers s. 18, 50 ... 

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