Cysteine alkylation

The other simple peptide complex e.g. [Fe(Z-Cys-Ala-OMe)4]2- did not exhibit such a reversible redox couple under similar conditions. The Fe(lll) complexes of simple peptide thiolates or cysteine alkyl esters are found to be thermally quite unstable and decompose by oxidaticxi at the thiolate ligand by intramolecular electron transfer. Thus the macro-ring chelation of the Cys-Pro-Leu-Cys ligand appears to stabilize the Fe(in) state. The stability of the Fe(ni) form as indicated by the cyclic voltamnoogram measurements and by the visible spectra of the Fe(in) peptide complexes suggests that the peptide prevents thermal and hydrolytic decomposition of the Fe-S bond because of the hydrophobicity and steric bulk of the Pro and Leu residues (3,4). 

The described conditions alkylate cysteine residues almost quantitatively, even for defensins, which contain three disulfide bonds. Higher temperatures (>37°C) and longer reaction times (> 1 h) do not further increase the cysteine alkylation but may produce further byproducts, such as carboxymethyllysine (CML). 

Thiazolidines Thiazolidines of some a,P-unsaturated 3-ketone steroids including progesterone, testosterone, and hydrocortisone (112, 113) were prepared from the reaction with cysteine alkyl esters and cysteamines as potential prodrugs.67,68 The thiazolidines readily reverted to their parent steroidal ketones,... 

A. Phage Cro protein has been ctmverted into an operator-specific nuclease by replacing the C-terminal alanine of the wild type protein with cysteine. Alkylation of the sulphydryl group with S-(iodoacetamido)-i,10-phenanthroline resulted in a semisynthetic nuclease which... 

HO C-CH (NH ) - (CH ) -CONH-CH (CH SH) -CONH-CH -COOH S-deprotonated L-cysteine alkyl ester... 

UDP-NAM synthase and protect the enzyme against inactivation by cysteine-alkylating agents. ... 

Organosulfur Adsorbates on Metal and Semiconductor Surfaces. Sulfur compounds (qv) and selenium compounds (qv) have a strong affinity for transition metal surfaces (206—211). The number of reported surface-active organosulfur compounds that form monolayers on gold includes di- -alkyl sulfide (212,213), di- -alkyl disulfides (108), thiophenols (214,215), mercaptopyridines (216), mercaptoanilines (217), thiophenes (217), cysteines (218,219), xanthates (220), thiocarbaminates (220), thiocarbamates (221), thioureas (222), mercaptoimidazoles (223—225), and alkaneselenoles (226) (Fig. 11). However, the most studied, and probably most understood, SAM is that of alkanethiolates on Au(lll) surfaces. 

When cysteine reacts with an alkyl or aiyl chloroformate, both the —SH and —NH groups are protected as a thiocarbonate and as a carbamate, respectively. Selective or simultaneous removal of the protective groups is possible. 

S,N-Ditrityl-L-cysteine diethylamine selt L-Tyrosine lower alkyl ester L-lsoleucine lower alkyl ester Benzyl-L-proline hydrochloride L-Leucine lower alkyl ester Ammonia Hydrogen chloride Glycine lower alkyl ester... 

British investigators (Haddow and Timmis 1951) synthesized and studied esters of the methanesulfonic acid. The most active derivative was the dimethylsulfonic ester of 1,4-butanedione, known as busulfan. Busulfan interacts with the thiol groups of proteins and amino acids some of its metabolites can alkylate the thiols of cysteine, peptides and proteins. Busulfan exerts selective cytotoxic activity in hematopoietic bone marrow cells and inhibits the formation of granulocytes and platelets. It slightly affects the lymphoid tissue. 

FIGURE 7. The reactions of OH radical with alkyl-L-cysteine sulfoxide. 

Nordberg J et ai Mammalian thioredoxin reductase is irreversibly inhibited by dinitrohaiobenzenes by alkylation of both the redox active selenocysteine and its neighboring cysteine residue.) Biol Chem 1998 273 10835. 

Chemical modifications like alkylation with (A-ethylmaleimide (NEM) or oxidation with diamide that inhibit the phosphorylation activity of the enzyme did not seem to have any significant effect on the high affinity binding site when the enzyme was solubilized in the detergent decyl-PEG [69,41]. However, in the intact membrane these treatments reduced the affinity by a factor of 2-3. The reduction of the affinity was exclusively due to modification of the cysteine residue at position 384 in the B domain [69]. Apparently, the detergent effects the interaction between the B and C domains. 

These workers have developed another new type of chiral S/N ligands, namely aziridine sulfides, which were easily synthesised in a straightforward synthetic route from inexpensive and readily available (i )-cysteine. The efficiency of this sterically and electronically varied set of ligands was then examined as chiral catalysts in the palladium-catalysed test reaction. The alkylated product was obtained in excellent yields and stereoselectivities of up to 99% ee, as shown in Scheme 1.44. 

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