Branched PEG remodeling and glycosylation of glucagon-like peptide-1 [GLP-1]

摘要

The present invention provides polypeptides that include an O-linked glycoconjugate in which a species such as a water-soluble polymer, a therapeutic agent of a biomolecule is covalently linked through an intact O-linked glycosyl residue to the polypeptide. The polypeptides of the invention include wild-type peptides and mutant peptides that include an O-linked glycosylation site that is not present in the wild-type peptide. Also provided are methods of making the peptides of the invention and methods, pharmaceutical compositions containing the peptides and methods of treating, ameliorating or preventing diseased in mammals by administering an amount of a peptide of the invention sufficient to achieve the desired response.

主权项

1. A mutant glucagon-like peptide-1 (GLP-1)-glucagon-like peptide-2 (GLP-2) fusion peptide of formula wherein AA is an amino acid with a side chain that comprises a hydroxyl moiety; wherein X is a modifying group or a saccharyl moiety; and wherein the mutant GLP-1-GLP-2 fusion peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 54-73.