Sulfur-cysteine reactions

After exposure to an oxidant, the potential types of oxidation products in proteins and peptides can be extensive (Stadtman and Fevine, 2000). Cysteine and methionine undergo a variety of sulfur oxidation reactions to yield cysteine disulfides, methionine sulfoxide, methionine... 

Structures of this type were generated in the reaction of Af-acyloxy-Af-alkoxyamides with thiols. Treatment of Ai-acetoxy-iV-butoxybenzamide (145, R = Bu, = Me) and a series of Ai-benzoyloxy-Ai-benzyloxybenzamides (139) with cysteine derivatives generated disulfides and hydroxamic esters (Section IV.C.3.b, Scheme 24). The intermediate Ai-alkoxy-Ai-thioalkylamides were unstable under the reaction conditions, reacting with a second thiol molecule at sulfur. The reaction of thiols at the anomeric nitrogen of Af-acyloxy-Ai-alkoxyamides has been modelled theoretically and is predicted to be favourable energetically, leading to a stable substitution product ... 

An ingenious procedure for replacing sulfur in a thiolactam by a -CH COR group involves alkylation of sulfur with an a-haloketone, followed by sulfur extrusion either with triphenyl phosphine or by heating in DMF (with or without added sodium ethoxide). Th reaction has been successfully applied thus far to isoqu oline-l(2H)-thione, quinazoline-4(3H)-thlone, and 6-mercaptopurine. A closely related intramolecular sulfur displacement reaction with intriguing synthetic potential is Illustrated by the conversion of the S-alkylation product from 6-chloropurine ribonucleosld gand cysteine to the isomeric N-alkylated product by treatment with alkali. 

Attachment to Sulfur Groups. Of all the amino acids, the two most reactive in solution toward the electron are cystine and cysteine. Reaction with the former leads to the disulfide anion radical,... 

The side groups of the amino acids vary markedly in size and chemical nature and play an important role in the chemical reactions of the fiber. For example, the basic groups (hisidine, arginine, and lysine) can attract acid (anionic) dyes, and in addition the side chains of lysine and hisidine are important sites for the attachment of reactive dyes. The sulfur-containing amino acid cysteine plays a very important role, because almost all of the cysteine residues in the fiber are linked in pairs to form cystine residues, which provide a disulfide bridge —S—S— between different polypeptide molecules or between segments of the same molecules as shown ... 

Displacement of the sulfhydryl group in primary thiols, like L cysteine and 2-diethylaminoethanethiol, requires elemental fluorine, the most active oxidant Elemental sulfur is the major by-product in those reactions [7] (equation 2)... 

FIGURE 20.7 (a) The aconitase reaction converts citrate to cis-aconitate and then to isocitrate. Aconitase is stereospecific and removes the pro-/ hydrogen from the pro-/ arm of citrate, (b) The active site of aconitase. The iron-sulfur cluster (red) is coordinated by cysteines (yellow) and isocitrate (white). 

These sulfides are prepared from other sulfur-protected cysteine derivatives by reaction with the sulfenyl chloride, The Npys group can also be introduced directly by treatment of the thiol with NpysCl, ... 

Reactions between A -(l-chloroalkyl)pyridinium chlorides 33 and amino acids in organic solvents have a low synthetic value because of the low solubility of the amine partner. A special protocol has been designed and tested in order to circumvent this drawback. Soon after the preparation of the salt, an aqueous solution of the amino acid was introduced in the reaction medium and the two-phase system obtained was heated under reflux for several hours. However, this was not too successful because sulfur dioxide, evolved during the preparation of the salt, was converted into sulfite that acted as an 5-nucleophile. As a result, A -(l-sulfonatoalkyl)pyridinium betaines such as 53 were obtained (Section IV,B,3) (97BSB383). To avoid the formation of such betaines, the salts 33 were isolated and reacted with an aqueous solution of L-cysteine (80) to afford thiazolidine-4-carboxylic acids hydrochlorides 81 (60-80% yields). 

Iron-sulfur proteins. In an iroinsulfiir protein, the metal center is surrounded by a group of sulfur donor atoms in a tetrahedral environment. Box 14-2 describes the roles that iron-sulfur proteins play in nitrogenase, and Figure 20-30 shows the structures about the metal in three different types of iron-sulfur redox centers. One type (Figure 20-30a l contains a single iron atom bound to four cysteine ligands. The electron transfer reactions at these centers... 

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