Thioester, determination

Derivatives with various substituted sulfonamides have been developed and used to form enolates from esters and thioesters.137 An additional feature of this chiral auxiliary is the ability to select for syn or anti products, depending upon choice of reagents and reaction conditions. The reactions proceed through an acyclic TS, and diastereoselectivity is determined by whether the E- or Z-enolate is formed.138 /-Butyl esters give A-enolates and anti adducts, whereas phenylthiol esters give syn adducts.136... 

The physiologist de Duve concentrated his efforts on a material link between the prebiotic phase of the primeval Earth and the state of development at which RNA (or a similar type of molecule) determined the further progress of the evolution process. In particular, this connecting link needed to have been able to transfer chemical energy, since without such a procedure, the RNA synthesis appears impossible. The molecular species which Christian de Duve favours for this important function is that of the thioesters. The exact reasoning as to why this is the case is discussed in detail in his book Vital Dust Life As a Cosmic Imperative (de Duve, 1996). 

Mammalian esterases have been classified into three groups according to specificity for substates and inhibitors (110). In terms of overall hydrolytic activity in mammals, the most important class of esterases is that of the B-esterases, which are principally active with aliphatic esters and amides. A-Esterases are important for aromatic esters and organophosphorus esters, and C-esterases are active with acetyl esters. In general, the specificity of mammalian esterases is determined by the nature of substituent groups (acetyl, alkyl, or aryl) rather than the heteroatom (O, N, or S) that is adjacent to the carboxy group. That is, the same esterase would likely catalyze hydrolysis of an ester, amide, or thioester as long as the substituents were identical except for the heteroatom (110). 

Sulfoxidation reactions are characterized by enzymatic conversion of a divalent compound to sulfoxide (Fig. 15.7) or, in some cases, to sulfone (S SO O ). The degradation also may be catalyzed by minerals, converting organic sulfides (thioesters) and sulfites to the corresponding sulfoxides and sulfates. Because it is difficult to determine if the reaction is chemically or biologically induced, microbially mediated sulfoxidation in the subsurface environment can be established only when a biocatalyst is found. 

Scheme 11 Determination of the relative stereochemistry of a P-amino thioester...

As discussed for N-myristoylation and S-prenylation, even S-acylation of proteins with a fatty acid which in the vast majority of cases is the C16 0 palmitic acid, plays a fundamental role in the cellular signal-transduction process (Table l). 2-5 14 While N-myristoylation and S-prenylation are permanent protein modifications due to the amide- and sulfide-type linkage, the thioester bond between palmitic acid and the peptide chain is rather labile and palmi-toylation is referred to as a dynamic modification. 64 This reversibility plays a crucial role in the modulation of protein functions since the presence or absence of a palmitoyl chain can determine the membrane localization of the protein and can also be used to regulate the interactions of these proteins with other proteins. Furthermore, a unique consensus sequence for protein palmitoylation has not been found, in contrast to the strict consensus sequences required for N-myristoylation and S-prenylation. Palmitoylation can occur at N- or C-terminal parts of the polypeptide chain depending on the protein family and often coexists with other types of lipidation (see Section 6.4.1.4). Given the diversity of protein sequences... 

An HPLC method was developed and validated for the determination and quantitation of both DFC cysteine and glutathione conjugates. This method was based on a cleavage of the disulphide and/or thioester bonds between the metabolites and their conjugate sulphur-containing moiety using dithioerythritol to yield DFC, which was then stabilized by derivatizing to DFC acetamide (91). 

Fenton SS, Fahey RC (1986) Analysis of biological thiols determination of thiol components of disulfides and thioesters. Anal Biochem 154 34-42... 

A method for the controlled emulsion polymerization of chloroprene using dithiocarbamic esters as sulfur-based chain transfer agents is described. The method provides industrially relevant molar masses with Mn s> 50,000 daltons with good yields in acceptable times. It was further determined that when pKa values for the dithiocarbamic acid precursors were less than 12, the thioester was ineffective as a regulator. 

The peanut chalcone synthase and parsley stilbene synthases have been cloned, expressed in E. colt, and purified to homogeneity [135,137]. The enzymes appear to be mechanistically similar each catalyzes the formation of a tetraketide from three molecules of malonyl CoA that are decarboxylated and condensed with a starter unit derived from p-coumaroyl CoA or a similar CoA thioester (Fig. 6). No reductions or dehydrations occur during either chalcone or stilbene synthesis, and some products spontaneously cyclize following their release from the enzyme. A major feature that distinguishes chalcone and stilbene synthases is that the latter perform an additional decarboxylation to remove a carbon atom that is present in chalcone products [132,138]. The presence of this additional carboxyl group results in a different cyclization pattern for chalcone products. The precise mechanisms by which chalcone and stilbene synthases determine the fate of this carbon atom are not known. 

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