Improved native chemical ligation with three or more components

Details Improved native chemical ligation with three or more components Improved native chemical ligation with three or more components

C - Chemistry, Metallurgy

07

K

C07K 1/02 (2006.01)

Patent

CA 2446152

The invention provides a method of assembling oligopeptide intermediates in a native chemical ligation reaction that eliminates self-ligation of bi- functional intermediates. An important aspect of the invention is a bi- functional intermediate with an N-terminal cyclic thiazolidine protecting group which effectively prevents self-ligation in the chemical assembly process. The present invention is useful in methods for convergent synthesis of polypeptides and proteins and improves the efficiency of native chemical ligation reactions, particularly where three or more peptide fragements are used to assemble a polypeptide or protein product.

L'invention concerne un procédé permettant d'assembler des intermédiaires oligopeptidiques dans une réaction de ligation chimique native, qui élimine l'auto-ligation d'intermédiaires bifonctionnels. Un aspect important de l'invention est un intermédiaire bifonctionnel à groupe thiazolidine cyclique N-terminal protecteur, qui prévient efficacement l'auto-ligation dans le processus d'assemblage chimique. L'invention s'utilise dans des procédés de synthèse convergente de polypeptides et de protéines et renforce l'efficacité de réactions de ligation chimique native, en particulier dans les cas où au moins trois fragments peptidiques sont utilisés pour assembler un produit polypeptidique ou protéinique.

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