Extended native chemical ligation of three or more peptide...

C - Chemistry – Metallurgy – 07 – K

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C07K 1/06 (2006.01) C07K 1/00 (2006.01) C07K 1/02 (2006.01) C07K 1/04 (2006.01) C07K 1/107 (2006.01) C07K 2/00 (2006.01)

Patent

CA 2466746

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 heterocyclic 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 fragments are used to assemble a polypeptide or protein product.

L'invention concerne une méthode destinée à assembler des intermédiaires oligopeptidiques au moyen d'une réaction de ligation chimique permettant de supprimer l'auto-ligation d'intermédiaires bifonctionnels. L'invention se rapporte notamment à un intermédiaire bifonctionnel renfermant un groupe protecteur hétérocyclique N-terminal qui empêche efficacement l'auto-ligation au cours du processus d'assemblage chimique. La présente invention est utile dans des méthodes de synthèse convergente de polypeptides et de protéines, et permet d'améliorer l'efficacité des réactions de ligation chimique native, notamment lorsqu'au moins trois fragments peptidiques sont utilisés pour assembler un produit polypeptidique ou protéique.

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