High-throughput synthesis of peptide alpha-thioesters: a safety catch linker approach enabling parallel hydrogen fluoride cleavage

Brust, Andreas, Schroeder, Christina I. and Alewood, Paul F. (2014) High-throughput synthesis of peptide alpha-thioesters: a safety catch linker approach enabling parallel hydrogen fluoride cleavage. ChemMedChem, 9 5: 1038-1046. doi:10.1002/cmdc.201300524


Author Brust, Andreas
Schroeder, Christina I.
Alewood, Paul F.
Title High-throughput synthesis of peptide alpha-thioesters: a safety catch linker approach enabling parallel hydrogen fluoride cleavage
Formatted title
High-throughput synthesis of peptide α-thioesters: a safety catch linker approach enabling parallel hydrogen fluoride cleavage
Journal name ChemMedChem   Check publisher's open access policy
ISSN 1860-7179
1860-7187
Publication date 2014-05
Sub-type Article (original research)
DOI 10.1002/cmdc.201300524
Open Access Status
Volume 9
Issue 5
Start page 1038
End page 1046
Total pages 9
Place of publication Weinheim, Germany
Publisher Wiley - V C H Verlag
Collection year 2015
Language eng
Formatted abstract
Peptide α-thioesters are fundamental building blocks in peptide and protein science, providing powerful tools for peptide medicinal chemistry. The application of peptide α-thioesters in native chemical ligation reactions has enabled synthetic access to cysteine-rich peptides and proteins, cyclic peptides as well as labeled and chemically modified biomolecules. An efficient high-throughput synthesis of peptide α-thioester building blocks would be beneficial for many medicinal chemical applications that require peptides and proteins. Herein we present a novel synthetic route to cysteine-rich peptide α-thioesters using a safety catch linker that enables a parallel synthetic strategy for chemical protein synthesis. ACP(68–75), bradykinin and dynorphin(1–13) were synthesized via Boc chemistry in their thioester form on a safety catch amide linker (SCAL), employing polystyrene- or poly(ethylene glycol)-based resins, compartmentalized in tea bags. This compartmentalized resin/linker strategy facilitated a parallel hydrogen fluoride cleavage in which each peptide thioester was subsequently cyclized by native chemical ligation, demonstrating the utility of this approach. A naturally occurring bioactive cyclic peptide, the sunflower trypsin inhibitor SFTI-1, was synthesized to demonstrate the viability of this method to access important peptide biomolecules.
Keyword Boc chemistry
High-throughput synthesis
Peptides
Solid-phase synthesis
Thioesters
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
Institute for Molecular Bioscience - Publications
 
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Created: Thu, 10 Apr 2014, 10:53:55 EST by Susan Allen on behalf of Institute for Molecular Bioscience