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The peptides in which the serine and/or threonine residues are isomerized from amide to ester (with their side chain hydroxyl group) are called O-acylisopeptides.
O-Acylisopeptides show distinct properties from the corresponding native peptides. They can also be converted to the native sequence in aqueous solutions at neutral pH.
The high water solubility of O-acylisopeptides makes them useful in various applications, including the synthesis of difficult hydrophobic sequences, convergent peptide synthesis, and controlled activation of some protein functions.
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<General Review of Chemical Synthesis of Peptides/Proteins>
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The use of special protecting groups enables the O-to-N rearrangement by external stimuli other than pH. In the example shown below, β-amyloid is converted to the native sequence by photo-irradiation.
- Serine residues are usually used as Boc-protected forms and cleaved/isolated from the solid phase as TFA salts.
- O-Acylated residues can be introduced by solid phase O-acylation under condensation conditions. However, esterification is often less efficient than amidation and racemization can also become problematic. It is usually more reliable to use preformed dipeptide units (Boc-Ser/Thr-(Fmoc-Xaa)-OH) which already contain an ester.
 Kiso, Y. et al. J. Am. Chem. Soc. 2006, 128, 696. DOI: 10.1021/ja057100v