Boc-solid phase peptide synthesis is useful for the preparation of peptide--thioesters. However, this strategy usually employs hydrogen fluoride for the final deprotection step. These strongly acidic conditions cannot be applied for the synthesis of acid-labile glycopeptide--thioesters. The protocol presented here is a modified in situ neutralization Boc-solid phase peptide synthesis employing 10% sulfuric acid/dioxane conditions for intermediate Boc removal and TfOH for the final side-chain deprotection step. These conditions were found to be applicable for the synthesis of acid-labile glycopeptide--thioesters. In this protocol, a glycopeptide is synthesized as thioester on a thiol linker, and the product glycopeptide--thioester is released from the resin by thiolysis after side-chain deprotection step with an acid cocktail containing TfOH instead of hydrogen fluoride. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.
The glycopeptide-thioesters are the key components for chemical synthesis of glycoproteins. We report a general procedure for the preparation of glycopeptide-thioesters employing a safe and efficient Boc-solid phase peptide synthesis using 10% sulfuric acid/dioxane for Boc deprotection, low-acidity TfOH conditions for global deprotection, and thiolysis for release of the thioester from the resin.