Abstract
The O-acyl isopeptide method was developed for the preparation of difficult sequence-containing peptides, whose hydrophobic nature hampers both peptide chain construction on resin and purification with HPLC after deprotection. In the O-acyl isopeptide method, the target peptide is synthesized in an O-acyl isopeptide form, which contains an O-acyl isopeptide bond instead of the native N-acyl peptide bond at a hydroxy group-containing amino acid residue, such as Ser or Thr. The hydrophilic O-acyl isopeptide can be isolated, e.g., as a lyophilized TFA salt. The target peptide can be quantitatively obtained by a final O-to-N intramolecular acyl migration reaction with exposure to neutral conditions. Additionally, the O-acyl isopeptide is important as a hydrophilic precursor peptide for biological peptide assays that are difficult to handle. This chapter describes the synthesis of such O-acyl isopeptides by stepwise and convergent Fmoc solid-phase peptide synthesis.
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Acknowledgments
We thank Yoshiaki Kiso for his mentorship and inspiration.
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Yoshiya, T. (2020). Synthesis of O-Acyl Isopeptides: Stepwise and Convergent Solid-Phase Synthesis. In: Hussein, W., Skwarczynski, M., Toth, I. (eds) Peptide Synthesis. Methods in Molecular Biology, vol 2103. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0227-0_8
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DOI: https://doi.org/10.1007/978-1-0716-0227-0_8
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