Cysteine scavengers

The reaction has been widely investigated for its synthetical relevance, due to the wide range of reagents that may be employed and to the possibility of ftiriher reactions of the products so obtained, as observed, for example, in the synthesis of diazoalkanes. It is also used in biological studies with cysteine scavengers and in several different applications, which are described in the appropriate chapters. 

Nishimura and coworkers57-59 studied the y-radiolysis of aqueous solutions of sulfoxide amino acids. Sulfoxide amino acids are the precursors of the flavors of onions (S-propyl-L-cysteine sulfoxide, S-methyl-L-cysteine sulfoxide and S-(l-propenyl)-L-cysteine sulfoxide) and garlic (S-allyl-L-cysteine sulfoxide). In studies on sprout inhibition of onion by /-irradiation it was found that the characteristic flavor of onions became milder. In the y-radiolysis of an aqueous solution of S-propyl-L-cysteine sulfoxide (PCSO)57,58 they identified as the main products alanine, cysteic acid, dipropyl disulfide and dipropyl sulfide. In the radiolysis of S-allyl-L-cysteine sulfoxide (ACSO) they found that the main products are S-allyl-L-cysteine, cysteic acid, cystine, allyl alcohol, propyl allyl sulfide and diallyl sulfide. The mechanisms of formation of the products were partly elucidated by the study of the radiolysis in the presence of N20 and Br- as eaq - and OH radicals scavengers, respectively. 

Paracetamol-induced hepatotoxicity can be prevented in animals with SOD, catalase and allopurinol (Kyle et al., 1987 Jaeschke, 1990 Tirmenstein and Nelson, 1990), and by N-acetyl-L-cysteine or methionine in humans (Meredith et al., 1986 Nelson, 1990). The protective efiect of allopurinol in mice only occurred at high concentrations, suggesting that its effect was related to scavenging of ROMs rather than inhibition of their production by XO (Jaeschke, 1990). 

Despite the conclusions in the cited literature about direct MT interaction with free radicals, the mechanism of MT antioxidant activity remains obscure. Markant and Pallauf [339] concluded that cysteine groups and not zinc are responsible for the inhibition of lipid peroxidation in hepatocytes. Maret and Vallee [340,341] also questioned the possibility of direct scavenging of free radicals by MT and suggested that zinc release is a major mechanism of antioxidant effects of metallothioneins. 

Protection against cell damage due to oxidative stress is provided, amongst others, by glutathione (GSH), a cellular tripeptide with a thiol function in a cysteine residue. GSH is deprotonated to GS, which is a scavenger for electrophilic compounds and is reduced to GS SG in defense of reactive oxygen species [28]. 

Trifluoroacetic acid removes tert-butyl-based protectors by the S vl mechanism, with the cation being trapped by the trifluoroacetate anion however, the tert-butyl trifluoroacetate produced is an alkylating agent, and the acid is not strong enough to protonate the side chains of methionine, tryptophan, and cysteine, so these are acceptors of tert-butyl. A scavenger is required to prevent their alkylation. Anisole... 

Alternatively to using prelipidated building blocks palmitoylation on resin is possible with the hydrazine linker. In Scheme 27 the synthesis route for the palmitoylated and farnesylated N-Ras peptide 78 is shown. Here the initial loading of trityl-protected cysteine to the hydrazine linker was mediated by A,A-diisopropylcarbodiimide (DIG) and HOBt. After Fmoc removal the proline was coupled using HBTU and HOBt. The trityl-protected dipeptide 75 was subsequently S-deprotected using TFA with triethylsilane (TES) as a scavenger. Farnesylation of the free thiol was achieved with an excess of farnesyl bromide. 

The 4-methoxybenzyl group is removed with 1 M TMSBr or 1M TMSOTf in TFA containing thioanisole and m-cresol as scavengers, that is, it is performed under identical conditions to those reported for the related cysteine derivative. 7 The Mob group is removed more efficiently by the DMSO/TFA method, which leads to formation of the diselenide as discussed in Section 6.2.3.I.2. 

---