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HF-Free Boc synthesis of peptide thioesters for ligation and cyclization

Abstract:
We have developed a convenient method for the direct synthesis of peptide thioesters, versatile intermediates for peptide ligation and cyclic peptide synthesis. The technology uses a modified Boc SPPS strategy that avoids the use of anhydrous HF. Boc in situ neutralization protocols are used in combination with Merrifield hydroxymethyl resin and TFA/TMSBr cleavage. Avoiding HF extends the scope of Boc SPPS to post-translational modifications that are compatible with the milder cleavage conditions, demonstrated here with the synthesis of the phosphorylated protein CHK2. Peptide thioesters give easy, direct, access to cyclic peptides, illustrated by the synthesis of cyclorasin, a KRAS inhibitor.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1002/anie.201607657

Authors


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Institution:
University of Oxford
Division:
MSD
Department:
Paediatrics
Role:
Author
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Role:
Author
ORCID:
0000-0002-6042-680X
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Role:
Author
ORCID:
0000-0002-5616-2143
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Role:
Author
ORCID:
0000-0002-2331-4729
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Role:
Author
ORCID:
0000-0003-1525-7768


Publisher:
Wiley
Journal:
Angewandte Chemie International Edition More from this journal
Volume:
55
Issue:
42
Pages:
13174-13179
Publication date:
2016-10-06
Acceptance date:
2016-09-02
DOI:
EISSN:
1521-3773
ISSN:
1433-7851


Language:
English
Keywords:
Pubs id:
1111522
Local pid:
pubs:1111522
Deposit date:
2020-06-11

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