Side-Chain Anchoring Strategies for the Synthesis of Peptide Thioesters and Selenoesters

Lucas Kambanis; Sameer S Kulkarni; Richard J Payne

doi:10.1007/978-1-0716-2489-0_9

Side-Chain Anchoring Strategies for the Synthesis of Peptide Thioesters and Selenoesters

Methods Mol Biol. 2022:2530:125-140. doi: 10.1007/978-1-0716-2489-0_9.

Authors

Lucas Kambanis^{1

2}, Sameer S Kulkarni^{1

2}, Richard J Payne³

Affiliations

¹ School of Chemistry, The University of Sydney, Sydney, NSW, Australia.
² Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, The University of Sydney, Sydney, NSW, Australia.
³ Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, The University of Sydney, Sydney, NSW, Australia. richard.payne@sydney.edu.au.

PMID: 35761046
DOI: 10.1007/978-1-0716-2489-0_9

Abstract

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.

Keywords: Chemical protein synthesis; Ligation; Selenoester; Selenoesterification; Side-chain; Side-chain anchored; Synthetic proteins; Thioester; Thioesterification.

MeSH terms

Peptides* / chemistry
Proteins
Solid-Phase Synthesis Techniques* / methods
Sulfur Compounds / chemistry

Substances

Peptides
Proteins
Sulfur Compounds