Thiol side chain

In line with the above-mentioned reactivity of cysteine thioesters is the occurrence of a S, N-acyl shift of the palmitoyl group from the thiol side chain to the a-amino group, when this amino group is present as a free amine. 

The sulfur atom is a favorable zinc ligand because of its size and polarizability. The thiol side chain of cysteine (p/Cg —8.5) is negatively charged as it complexes a metal ion in a protein in addition to metal coordination, the cysteine thiol may simultaneously accept hydrogen bonds from other protein residues (Adman et al, 1975 Ippolito et al, 1990). Hydrogen bond networks with cysteine metal ligands are discussed further in Section I11,B. 

Cu(II) has been shown to be bound by two cysteines [32]. The main limitation of the use of cysteine or glutathione for detecting metal ions is the thiol side chain which having a high affinity for soft metals is being employed to immobilise the peptide and hence is not available for coordination with the metal ion. 

Several different amino acid side chains can act as nucleophiles in enzyme catalysis. The most powerful nucleophile is the thiol side chain of cysteine, which can be deproto-nated to form the even more nucleophilic thiolate anion. One example in which cysteine is used as a nucleophile is the enzyme glyceraldehyde 3-phosphate dehydrogenase, which uses the redox coenzyme NAD+. As shown in Fig. 10, the aldehyde substrate is attacked by an active site cysteine, Cys-149, to form a hemi-thioketal intermediate, which transfers hydride to NAD+ to form an oxidized thioester intermediate (7). Attack of phosphate anion generates an energy-rich intermediate 3-phosphoglycerate. 

Cephalosporins that contain a methyltetrazole-thiol side chain (as in cefamandole, cefmenoxime, cefmeta-zole, cefonizid, cefoperazone, ceforanide, cefotetan, cefotiam, latamoxef, and moxalactam) and chemically similar structures (cefepime, ceftriaxone) co-adminis-tered with alcohol can produce a disulfiram-like syndrome by inhibiting aldehyde dehydrogenase (195,202,203). 

Originally the technique was restricted to proteins having adventitiously exposed histidyl or thiol side-chain groups that can bind to the Mn(IMAC) site.1,82-87 However, the attachment of polyhistidine affinity tails (His , n = 2 to 6) either as an N-terminal or a C-terminal fusion to a desired protein, affords a better binding site on it than any natural protein.88,89 This allows selective separation of the tagged protein. 

Derivatization of Cys is easily accomplished because of the highly nucleophilic nature of the thiol side chain. Use of the desired alkyl halide or tosylate under a variety of conditions (acidic, basic) or the relevant alcohol under acidic conditions generally gives good yields of the desired derivative [30,65,67-69,72,75,76,78-81,86-89] (Scheme 17). Protection with the Snm group can be accomplished by displacing the Acm group with (chlorocarbonyl) sulfenyl chloride followed by addition of A-methylaniline... 

Figure 5-13 A thioester at the C-terrninus of one peptide serves as the electrophile for bimolecular condensation with the thiol side chain of an N-terminal cysteine residue. The S,N-acy intramolecular rearrangement forms the native amide bond.

H2l-thioglycolate suggest that the dependence on thiol structure may be due to internal quenching of one radical site of the activated chromophore by the hydrogen atoms of the thiol side chain. A comparison of DNA damage produced by activation of the neocarzinostatin chromophore with several thiol activators revealed that the fragmentation pathway (i.e. the initial site... 

Acyclic sulfides with oxidized or thiol side-chains (Nos 1668,1675,1677,1688-1692,1703and... 

The Committee evaluated a group of flavouring substances consisting of 51 simple aliphatic and aromatic sulfides and thiols, which included 3 simple sulfides (Nos 1683, 1684 and 1707), 10 acyclic sulfides with oxidized and thiol side-chains (Nos 1668,1675, 1677, 1688-1692, 1703 and 1710), 1 heterocyclic sulfide (No. 1685), 5 thiols (Nos 1659 and 1662-1665), 12 thiols with oxidized side-chains (Nos 1666, 1667, 1669-1674, 1704-1706 and 1708), 3 dithiols (Nos 1660, 1661 and 1709), 7 disulfides (Nos 1693, 1694 and 1696-1700), 2 trisulfides (Nos 1695 and 1701), 2 heterocyclic disulfides (Nos 1686 and 1687) and 6 thioesters and acids (Nos 1676, 1678-1681 and 1702). The evaluations were conducted according to the Procedure for the Safety Evaluation of Flavouring Agents (see Figure 1, Introduction) (Annex 1, reference 131). None of these substances has previously been evaluated. 

Dithiahexane Acyclic sulfides with oxidized and thiol side-chains 1707 N No safety concern... 

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