Carbonyl groups thiols reacting with

As mentioned in the previous section, a,P-unsaturated carbonyl structures readily react with free sulfhydryl groups of low-molecular weight thiols and most probably also of proteins, since most proteins whose activity is affected by STL possess free cysteine groups (for an overview see [3]). 

Thiols react with the carbonyl group to form thioacetals... 

Analogously, aldehydes react with ammonia [7664-41-7] or primary amines to form Schiff bases. Subsequent reduction produces a new amine. The addition of hydrogen cyanide [74-90-8] sodium bisulfite [7631-90-5] amines, alcohols, or thiols to the carbonyl group usually requires the presence of a catalyst to assist in reaching the desired equilibrium product. 

Carbonyl compounds react with thiols, RSH, to form hemi-thioacetals and thioacetals, rather more readily than with ROH this reflects the greater nucleophilicity of sulphur compared with similarly situated oxygen. Thioacetals offer, with acetals, differential protection for the C=0 group as they are relatively stable to dilute acid they may, however, be decomposed readily by H20/HgCl2/CdC03. It is possible, using a thioacetal, to reverse the polarity of the carbonyl carbon atom in an aldehyde thereby converting this initially electrophilic centre into a nucleophilic one in the anion (31) ... 

Figure 1.70 AMBH is a hydrazide-containing compound that reacts with carbonyl groups to form hydrazone bonds. The free thiol can be used for subsequent conjugation reactions.

The Ras proteins were then allowed to react with the MIC-modified peptides in stoichiometric amounts. The maleimido group1261 reacts specifically with mercapto groups of proteins by conjugate addition of the thiol to the a, 3-unsaturated carbonyl compound. The Ras mutants reacted smoothly with the MIC modified peptides and in... 

The Michael reaction involves conjugate addition of a nucleophile onto an a,P-unsaturated carbonyl compound, or similar system. Such reactions take place in nature as well, and some can be potentially dangerous to us. For example, the a,P-unsaturated ester ethyl acrylate is a cancer suspect agent. This electrophile can react with biological nucleophiles and, in so doing, bind irreversibly to the nucleophile, rendering it unable to carry out its normal functions. A particularly important enzyme that can act as a nucleophile is DNA polymerase, which is responsible for the synthesis of strands of DNA, especially as part of a DNA repair mechanism (see Section 14.2.2). The nucleophilic centre is a thiol grouping, and this may react with ethyl acrylate as shown. 

Dithioketals, especially the cyclic dithiolanes and dithianes, are also useful carbonyl-protecting groups. These can be formed from the corresponding dithiols by Lewis acid-catalyzed reactions. The catalysts that are used include BF3, Mg(03SCF3)2, Zn(03SCF3)2, and LaCl3.100 S-Trimethylsilyl ethers of thiols and dithiols also react with ketones to form dithioketals.101... 

As already mentioned (see section 3.1) lipid peroxides can also break down non-enzymically to yield a variety of carbonyls, such as the hydroxyalkenals [54]. These aldehydes, and in particular 4-hydroxynonenal (HNE), can react with thiol and amino groups of nearby proteins, affecting several enzymic activities [55], These effects however appear to occur at HNE concentrations greater than 10 [lM. At low non-toxic concentrations other effects have been observed which have considerable relevance to cell proliferation. These include the stimulation of adenyl-cyclase and phospholipase C activity in liver membranes [56,57] and an inhibition of ornithine-decarboxylase activity [58] and the expression of globin genes and the protooncogene c-myc in K562 murine leukaemia cells [59]. 

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