| 摘要 |
The present invention provides fusion peptides having GLP-1 activity and enhanced stability in vivo, in particular resistancy to dipeptidyl peptidase IV conjugated to polymers, thereby forming conjugate molecules. The fusion peptide of the conjugate molecule comprises as component (I) N-terminally a GLP-1(7-35, 7-36 or 7-37) sequence and as component (II) Gterminally a peptide sequence of at least 9 amino acids or a functional fragment, variant or derivative thereof. A synthetic polymer and/or a protein, e.g transferrin or albumin, is covalently or non-covalently bound to the fusion peptide to form the conjugate molecule. Component (II) is preferably a full or partial version of IP2 (intervening peptide 2). A preferred embodiment comprises the sequence GLP-1(7-35, 36 or 37)/IP2/GLP-1(7-35, 36 or 37) or GLP-2 and a polymeric component, e.g. a natural or non-natural polymer. The fusion peptide may be produced in engineered cells or synthetically and is e.g. conjugated to the polymeric component by chemical synthesis. The conjugate molecule may be used for the preparation of a medicament for treating various diseases or disorders, e.g. diabetes type 1 or 2, apoptosis related diseases or neurodegenerative disorders.
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