Homocysteine thiolactone

In the preparation via diazotisation and bromination of homocysteine thiolactone, presence of unreacted diazo intermediate led to an explosion during distillation of the product. 

Modification of Amines with N-Acetyl Homocysteine Thiolactone... 

Thiolation of peptides and other small molecules containing amines proceeds easily with N-acetyl homocysteine thiolactone. However, protein modification often results in much lower yields unless the reaction is done for extended periods at pH 10-11. 

Add N-acetyl homocysteine thiolactone (Aldrich) to the bicarbonate reaction mixture to obtain a concentration representing a 10- to 20-fold excess over the amount of amines present. For protein thiolation, add the same molar excess of thiolactone reagent to the water reaction medium, and then slowly add an equivalent molar quantity of silver nitrate (AgNO j). Maintain the pH at 7.0-7.5 with periodic addition of NaOH. 

Figure 1.68 N-Acetyl homocysteine thiolactone spontaneously reacts with amine groups on proteins to create sulfhydryl groups.

Remove unreacted N-acetyl homocysteine thiolactone and reaction by-products by gel filtration or dialysis against lOmM sodium phosphate, 0.15M NaCl, lOmM EDTA, pH 7.2. Other buffers suitable for individual protein stability may be used as desired. For the silver nitrate-containing reaction, removal of the silver-thiourea complex may be done by adsorption onto Dowex 50, and the protein subsequently eluted from the resin by 1M thiourea. Removal of the thiourea then may be done by gel filtration or dialysis. 

Immobilized dihydrolipoamide (thioctic acid) (Gorecki and Patchornick, 1973 Gorecki and Patchornick, 1975) and immobilized N-acetyl-homocysteine thiolactone (Eldjarn and Jellum, 1963 Jellum, 1964) are the two most commonly used immobilized disulfide reductants. In addition, immobilized TCEP provides a reducing matrix that is free of thiols (Thermo Fisher). Such immobilized reductants successfully can be used to reduce many types of biological disulfides, including small molecules like oxidized glutathione and bovine insulin. They... 

Classic antioxidants, vitamin E, vitamin C, and others can suppress the activation of apoptosis. For example, ascorbic acid prevented cytochrome c release and caspase activation in human leukemia cells exposed to hydrogen peroxide [128], Pretreatment with A -acctylcystcinc, ascorbate, and vitamin E decreased homocysteine thiolactone-induced apoptosis in human promyelocytic leukemia HL-60 cells [129]. Resveratrol protected rat brain mitochondria from anoxia-reoxygenation damage by the inhibition of cytochrome c release and the reduction of superoxide production [130]. However, it should be mentioned that the proapoptotic effect of ascorbate, gallic acid, or epigallocatechin gallate has been shown in the same human promyelocytic leukemia cells [131]. 

Fig. 7.11. Metabolism of S-(l- [(2,3,4,5-tetrahydro-2-oxothiophen-3-yl)amino]carbonyl ethyl) thiophene-2-carbothioate (MR 889, 7.71) in rats to the active thiol metabolite homocysteine thiolactone thiolactamide (7.72) and to thiophene-2-carboxylic acid (7.73) [154], Subsequent reactions of hydrolysis and conjugation are also shown.

Amino acids (serine, proline, leucine), atenolol, norephedrine, homocysteine thiolactone RP-HPLC column coated with chiral Schiff base 1 mM CUSO4 in water 213... 

Homocysteine, HSCH2CH2CH(NH2)C02H, is a toxic amino acid that is thought to acylate lysine residues on proteins via its corresponding thiolactone (72) (Scheme 19). Now, for the first time, the kinetics have been studied of the aminolysis of (72) and of two model compounds, y-thiobutyrolactone (72 H instead of NH2) and N-trimethylamino homocysteine thiolactone (72 Me3N+ instead of NH2). A Brpnsted plot for homocysteine thiolactone (72) gave ft = 0.66. This and other data supported... 

Dihydro-2-oxo-3-pyridoxaminothiophen = Pyridoxal homocysteine thiolactone enamine167... 

Jakubowski, H. (2000). Calcium-dependent human serum homocysteine thiolactone hydrolase. A protective mechanism against protein N-homocysteinylation. J. Biol. Chem. 275 3957-62. 

H. Jakubowski, Metabolism of Homocysteine Thiolactone in Human Cell Cultures, Journal of Biological Chemistry 2 (1997) 1935-1942. 

E. Ferguson, N. Hogg, W. A. Antholine, J. Joseph, R. J. Singh, S. Parthasarathy, and B. Kalyanaraman, Characterization of the Adduct Formed from the Reaction Between Homocystein Thiolactone and Low-Density Lipoprotein Antioxidant Implications, Free Radical Biology and Medicine 26 (199 ) 968-977. 

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