Thioester general structure

A more versatile route to synthesize peptide thioesters is by the preparation of a peptide thioacid via the solid-phase method and then reaction with a halo derivative to form the thioester. This route can be achieved via the preparation of thioester linkers that can be applied in stepwise solid-phase peptide synthesis. The general structure of the N-protected amino thioacid attached to the linker is shown in Scheme 14. t65-80 ... 

In cells, such acylations occur with the sulfur analogue of an ester, called a thioester, having the general structure RCOSR. The most common thioester is called acetyl coenzyme A, often referred to merely as acetyl CoA. 

Thioester (Section 22.17) A compound with the general structure... 

Peptide thioesters (Section 15.1.10) are generally prepared by coupling protected amino acids or peptides with thiols and are used for enzymatic hydrolysis. Peptide dithioesters, used to study the structures of endothiopeptides (Section 15.1.11), may be prepared by the reaction of peptide nitriles with thiols followed by thiolysis (Pinner reaction). Peptide vinyl sulfones (Section 15.1.12), inhibitors of various cysteine proteases, are prepared from N-protected C-terminal aldehydes with sulfonylphosphonates. Peptide nitriles (Section 15.1.13) prepared by dehydration of peptide amides, acylation of a-amino nitriles, or the reaction of Mannich adducts with alkali cyanides, are relatively weak inhibitors of serine proteases. 

In a combined experimental/ah initio MO study, Bowie and coworkers144 addressed the questions concerning the reaction site of ambident nucleophiles with Me3Si4. It was demonstrated that the reaction of Me 3 Si4 with esters, thioesters, thionoesters, anhydrides and thioanhydrides of the general formula A-C(Y)-X-B (A, B alkyl B = CO-alkyl X, Y = O, S) two possible adducts 296 and 297 of comparable energies are formed. From the product observed under ICR conditions it was concluded that structure 297 serves as precursor for dissociation reactions no firm evidence was available to support the intermediacy of 296 in the decomposition chemistry of the encounter complexes. 

Recently, the structure of a putative third type of thioesterase from M. tuberculosis was determined.This enzyme, shown to be a long-chain fatty acyl-CoA thioesterase (FcoT), has a hotdog fold similar to type II thioesterases, but does not have a carboxylate in its active site that can act as a nucleophile or general base during catalysis. Instead, it has been suggested that hydroxide ions are formed in the active site which subsequently attack the thioester this mechanism is similar to the one described for the hydrolytic antibody D2.3, which have a similar active site architecture to that of FcoT. This difference in mechanism suggests that FcoT in fact represents a third type of thioesterase. 

The reactions that produce thioesters are essential in energy-harvesting pathways as a means of "activating" acyl groups for subsequent breakdown reactions. The complex thiol coenzyme A is the most important acyl group activator in the cell. The detailed structure of coenzyme A appears in Section 13.9, but it is generally abbreviated CoA—SH to emphasize the importance of the sulfhydryl group. The most common thioester is the acetyl ester, called acetyl coenzynne A (acetyl CoA). 

The thioester moiety in 225 (see 229) is formed by reaction of the phosphonate ester of the appropriate acid (see generic structure 228) with the thallium salt of 2-methyl-2-propanethiol [TlSC(Me)3], which is a mild and general procedure for the preparation of thioesters. 

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