Thiol-groups from oxidation

After removal of the S-Trityl groups by silver nitrate (Zervas, 1962), the free thiol groups were oxidized by diiodoethane (Weygand, 1962). Bty releasing the peptides obtained from the polymer by treatment with HBr in trifluoroacetic acid followed by purification on Dowex 50, E. Bondi of our department obtained an 80% overall yield of H2N Cys-Cys-AlaOH. 

Disulfides. As shown in Figure 4, the and h-chains of insulin are connected by two disulfide bridges and there is an intrachain cycHc disulfide link on the -chain (see Insulin and other antidiabetic drugs). Vasopressin [9034-50-8] and oxytocin [50-56-6] also contain disulfide links (48). Oxidation of thiols to disulfides and reduction of the latter back to thiols are quite common and important in biological systems, eg, cysteine to cystine or reduced Hpoic acid to oxidized Hpoic acid. Many enzymes depend on free SH groups for activation—deactivation reactions. The oxidation—reduction of glutathione (Glu-Cys-Gly) depends on the sulfhydryl group from cysteine. 

The reaction of hydroxyethyl-TPP with the oxidized form of lipoic acid yields the energy-rich thiol ester of reduced lipoic acid and results in oxidation of the hydroxyl-carbon of the two-carbon substrate unit (c). This is followed by nucleophilic attack by coenzyme A on the carbonyl-carbon (a characteristic feature of CoA chemistry). The result is transfer of the acetyl group from lipoic acid to CoA. The subsequent oxidation of lipoic acid is catalyzed by the FAD-dependent dihydrolipoyl dehydrogenase and NAD is reduced. 

The final step in the /3-oxidation cycle is the cleavage of the /3-ketoacyI-CoA. This reaction, catalyzed by thiolase (also known as j8-ketothiolase), involves the attack of a cysteine thiolate from the enzyme on the /3-carbonyI carbon, followed by cleavage to give the etiolate of acetyl-CoA and an enzyme-thioester intermediate (Figure 24.17). Subsequent attack by the thiol group of a second CoA and departure of the cysteine thiolate yields a new (shorter) acyl-CoA. If the reaction in Figure 24.17 is read in reverse, it is easy to see that it is a Claisen condensation—an attack of the etiolate anion of acetyl-CoA on a thioester. Despite the formation of a second thioester, this reaction has a very favorable A).q, and it drives the three previous reactions of /3-oxidation. 

Penicillamine reacts with pyridoxal-5-phosphate to form a thiazolidine derivative, and is able to displace many amino acids from their Schiff base complexes, forming stable compounds of this type. The reactivity of the thiol group of penicillamine is less than that of cysteine, probably because of steric hindrance by the adjacent methyl groups of penicillamine, which in consequence is less rapidly oxidized in vivo [7]. 

The thiol group was displaced from 3-mercapto-l,2,4-triazoles 59 using oxidation to yield the corresponding 3-unsubstituted compounds 60a-d in good yield (Equation 19) (Table 5) <2006S156>. 

The actual pathway by which fatty acid oxidation occurred was established by Lynen (1952-1953). Its unique and characteristic reaction was the thioclastic attack by coenzyme A on the B-ketoacyl CoA derivative, splitting off the 2C fragment, acetyl CoA. Free coenzyme A was very difficult to isolate and although it was synthesized in Todd s laboratory in Cambridge in the mid-1950s, much of the early work from Lynen s laboratory utilized A-acetyl cysteamine as a not very efficient (ca.1%) coenzyme A analogue. It carried the essential thiol group of the B-mercaptoethylamine end of CoA and could be used in most, but not all, of the steps in the spiral. 

Example Peptides often contain sulfur from cysteine. Provided there are at least two cysteines in the peptide molecule, the sulfur can be incorporated as thiol group (SH, reduced) or sulfur bridge (S-S, oxidized). Often, both forms are contained in the same sample. At ultrahigh-resolution, the contributions of these compositions to the same nominal m/z can be distinguished. The ultrahigh-resolution matrix-assisted laser desorption/ionization (MALDI) FT-ICR mass spectrum of native and reduced [D-Pen jenkephalin gives an example of such a separation (Fig. 3.25). [39] The left expanded view shows fully resolved peaks due to and C2 isotopomers of the native and the all- C peak of the reduced compound at m/z 648. The right expansion reveals the peak of the native plus the... 

A new method for the preparation of pyrrolo[2,l-c][l,4]benzothiazepine 292 starting from aldehyde 291 with an intramolecular Mitsunobu cyclization in the last step has been reported (Scheme 63 (1999T1479)). A disadvantage of this procedure is the redox nature of the Mitsunobu reaction, which is responsible for a side oxidation of the thiol group and poor isolated yields of the product. 

Mason (30) and Pierpoint (31) have described the involvement of o-diphenols in plants and how they contribute to abnormal plant pigmentation. o-Diphenols are oxidized to o-quinones by enzymes of the phenolase complex (o-diphenol O2 oxidoreductase, E.C. 1.10.3.1) and by peroxidase (E.C. 1.11.1.7). o-Quinones react with amino acids, proteins, amines and thiol groups of proteins to polymerize and from reddish-brown pigments. Concentrations of caffeic acid are doubled in both bean (8) and peanut... 

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