Site-specific GLP-2 conjugate using an immunoglobulin fragment

摘要

Provided are a glucagon-like peptide-2 (GLP-2) conjugate containing native GLP-2 or its derivative and an immunoglobulin Fc fragment being covalently linked via a non-peptidyl polymer, wherein the native GLP-2 or its derivative has a thiol group introduced at its C-terminal end, and one end of the non-peptidyl polymer is linked to an amino acid residue of the GLP-2 other than the N-terminal amino group thereof; a method for preparing the GLP-2 conjugate; a pharmaceutical composition comprising the same; and a method for treating or preventing intestinal disease, intestinal injury, or gastrosis by using the same. Since the GLP-2 conjugate of the present invention has a remarkably increased binding affinity to a GLP-2 receptor, it shows a prolonged in vivo half-life and an improved in vivo durability and stability.

主权项

1. A glucagon-like peptide-2 (GLP-2) conjugate comprising native GLP-2 or its derivative and an immunoglobulin Fc fragment being covalently linked via a non-peptidyl polymer, wherein the native GLP-2 or its derivative has a thiol group introduced at its C-terminal end, and one end of the non-peptidyl polymer is linked to the C-terminal thiol group of the GLP-2 or its derivative,
wherein the derivative of GLP-2 is selected from the group consisting of a GLP-2 derivative prepared by removing α-carbon of histidine which is the first amino acid at the N-terminal end of the native GLP-2 and an N-terminal amine group bound thereto; a GLP-2 derivative prepared by deleting an N-terminal amine group of the native GLP-2; a GLP-2 derivative prepared by substituting an N-terminal amine group of the native GLP-2 with a hydroxyl group; a GLP-2 derivative prepared by modifying an N-terminal amine group of the native GLP-2 with a dimethyl group; and a GLP-2 derivative prepared by substituting an N-terminal amine group of the native GLP-2 with a carboxyl group.