Side-Chain Anchoring Strategies for the Synthesis of Peptide Thioesters and Selenoesters
Kambanis, L.; Kulkarni, S.S.; Payne, R.J.
Methods in Molecular Biology 2530: 125-140
ISSN/ISBN: 1940-6029 PMID: 35761046 Accession: 080064529
Peptides bearing C-terminal thioester and selenoester functionalities are essential precursors for the chemical synthesis of larger proteins using ligation chemistry, including native chemical ligation (NCL) and diselenide-selenoester ligation (DSL). The use of a side-chain anchoring thioesterification or selenoesterification approach offers a robust method to access peptide thioesters or peptide selenoesters in excellent yields and in high purity. Importantly, this methodology overcomes solubility issues and epimerization of the C-terminal amino acid residue that can occur using solution-phase approaches. Detailed methods for the solid-phase synthesis of peptide thioesters and selenoesters using a side-chain anchoring approach are outlined in this article.