HF-free Boc synthesis of peptide thioesters for ligation and cyclization
Research output: Contribution to journal › Article
Colleges, School and Institutes
- Structural Biology Science Technology Platform, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.
- Département de Chimie, ENS, PSL Research University, UPMC, Univ Paris 06, CNRS, LBM, Paris, France.
- Merck Chemicals, Padge Road, Beeston, Notts, NG9 2JR, UK.
- The Francis Crick Institute, 1 Midland road, London, NW1 1AT, UK. email@example.com.
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.
|Number of pages||6|
|Journal||Angewandte Chemie (International Edition)|
|Early online date||6 Oct 2016|
|Publication status||Published - 10 Oct 2016|
- Cyclization, Esters/chemistry, Formic Acid Esters/chemical synthesis, Molecular Structure, Peptides/chemistry, Sulfhydryl Compounds/chemistry