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Gross, CM ; Lelièvre, D ; Woodward, CK ; Barany, G

Preparation of protected peptidyl thioester inter-mediates for native chemical ligation by N-a-9-fluorenylmethoxycarbonyl (Fmoc) chemistry : considerations of side-chain and backbone anchoring strategies, and compatible protection for N-terminal cysteine

Journal of Peptide Research 65 (3) 395-410

par Administrateur - publié le

Abstract :

Native chemical ligation has proven to be a powerful method for the synthesis of small proteins and the semisynthesis of larger ones. The essential synthetic intermediates, which are C-terminal peptide thioesters, cannot survive the repetitive piperidine deprotection steps of N-a-9-fluorenylmethoxycarbonyl (Fmoc) chemistry. Therefore, peptide scientists who prefer to not use N-a-t-butyloxycarbonyl (Boc) chemistry need to adopt more esoteric strategies and tactics in order to integrate ligation approaches with Fmoc chemistry. In the present work, side-chain and backbone anchoring strategies have been used to prepare the required suitably (partially) protected and/or activated peptide intermediates spanning the length of bovine pancreatic trypsin inhibitor (BPTI). Three separate strategies for managing the critical N-terminal cysteine residue have been developed :