Thioester exchange

Figure29-1. Partial reactions in the attachment of ubiquitin (UB) to proteins. (1) The terminal COOH of ubiquitin forms a thioester bond with an -SH of E, in a reaction driven by conversion of ATP to AMP and PP. Subsequent hydrolysis of PP by pyrophosphatase ensures that reaction 1 will proceed readily. (2) A thioester exchange reaction transfers activated ubiquitin to Ej. (3) E3 catalyzes transfer of ubiquitin to e-amino groups of lysyl residues of target proteins.

Woll, M. G. Gelhnan, S. H. Backbone thioester exchange A new approach to evalnating higher order structural stability in polypeptides. J. Am. Chem. Soc. 2004,126, 11172-11174. 

Recently, thiols have also been shown to participate in a series of new reversible reactions suitable for DCC. Such reactions include (1) the thioester exchange reaction (Fig. 6b), (2) the thiazolidine exchange reaction (Fig. 6c), and (3) the reversible Michael addition of thiols (Fig. 6d). 

Fig. 6 (a) Thiol-disulfide exchange, (b) Thiol-thioester exchange, (c) Thiazolidine exchange, (d) Reversible Michael addition of thiols... 

Figure 1 Relative Native Chemical Ligation Rates of C-Terminal Thioester Peptides Corresponding to L-Y-R-A-X (X is the designated amino acid) Percent Ligation Product (Filled Symbols) and Phenylmeth-anethiol-Thioester Exchange Intermediates (Unfilled Symbols) as a Function of Timel ...

The chemoselectivity of the reaction stems from the combination of a Cys specific, reversible thioester exchange (any Cys residue in either peptide can participate in this equilibrium) with an essentially irreversible intramolecular reaction that is specific to N-terminal Cys residues. Under typical ligation conditions (pH 6.5-7.5,1 mM peptide) the intermoleculartransthioesterification is rate limiting and no thioester intermediate is observed because of rapid rearrangement [47]. The reaction also utilizes the unique reactivity profile of the thioester as an activated acyl group. Compared to oxoesters with identical substituents, thioesters are much more reactive toward thiol nucleophiles [49] (and to a lesser extent toward amine nucleophiles [50]), facilitating rapid... 

Figures. Thiol-thioester exchange to form an amide bond. Nucleophilic attack takes place by the side chain thiol functionality in a cysteinyl peptide at a thioester segment to form an intramoiecular thioester, which undergoes intramolecular S N acyl transfer to form an amide bond.

The thermodynamically controlled amide exchange may be catalyzed by amido-alumtnum complexes in organic solvents however, the relatively high temperatures required (90-120 °C) represent a limitation for its use in DCLs of receptors [42, 43]. Alternatively, enzymeotalyzed transimination has been reported. Thioester exchange and amide exchange have not yet been explored for the preparation of DCLs of potential receptors. 

Figure 25 Backbone thioester exchange for the quantification of peptide folding interactions.

P.J. Bracher, P.W. Snyder, B.R. Bohall, G.M. Whitesides, The relative rates of thiol-thioester exchange and hydrolysis for alkyl and aryl thioalkanoates in water. Origins Life Evol. B 41, 399 12(2011)... 

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