HF-free Boc synthesis of peptide thioesters for ligation and cyclizationMore about Open Access at the Crick
Authors listRichard Raz Fabienne Burlina Soly Ismail Julian Downward Jiejin Li Stephen J Smerdon Martin Quibell Peter D White John Offer
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.
Issue number 42