Post-cleavage sulfur deprotection for convergent protein...

C - Chemistry – Metallurgy – 07 – K

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C07K 1/00 (2006.01) C07K 1/02 (2006.01) C07K 1/04 (2006.01) C07K 1/107 (2006.01)

Patent

CA 2487342

The present invention provides a method and compositions for synthesizing an oligopeptide or polypeptide by convergent assembly of a plurality of pairs of oligopeptides in chemical ligation reactions. An important aspect of the present invention is an oligopeptide having a C-terminal disulfide-protected carboxythioester group that can be deprotected to spontaneously generate a free C-terminal thioester moiety. This allows a single precursor to participate in a succession of chemical ligation reactions, thereby making the convergent synthesis approach possible. The present invention is useful in methods for chemical synthesis of oligopeptides, polypeptides and proteins, and improves the efficiency of native chemical ligation reactions, particularly where four or more peptide fragments are used to assemble an oligopeptide, polypeptide or protein product.

L'invention concerne un procédé et des compositions destinés à la synthèse d'un oligopeptide ou d'un polypeptide par un assemblage convergent de plusieurs paires d'oligopeptides dans des réactions de ligation chimique. Un aspect important de l'invention concerne un oligopeptide comportant un groupe carboxythioester, à disulfure protégé, en C-terminal qui peut être déprotégé afin de produire de façon spontanée une entité thioester en C-terminal libre. Un précurseur unique peut ainsi participer à une succession de réactions de ligation chimique, ce qui rend possible l'approche de synthèse convergente. Cette invention est utile dans des procédés de synthèse chimique d'oligopeptides, de polypeptides et de protéines, et améliore l'efficacité de réactions natives de ligation chimique, en particulier celles dans lesquelles on utilise quatre fragments peptidiques ou plus afin d'assembler un oligopeptide, un polypeptide ou une protéine.

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