Glucagon analogs exhibiting enhanced solubility and...

C - Chemistry – Metallurgy – 07 – K

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C07K 14/605 (2006.01) A61K 38/00 (2006.01) A61K 38/26 (2006.01) A61K 47/48 (2006.01) A61P 1/00 (2006.01) A61P 3/00 (2006.01) C07K 17/08 (2006.01)

Patent

CA 2727161

Modified glucagon peptides are disclosed having improved solubility and/or half--life while retaining glucagon agonist activity. The glycogen peptides have been modified by substi-tution of native amino acids with, and/or addition of, charged amino acids to the carboxy terminus of the peptide. The modified glucagon agonists can be further modified by pegylation, or the ad-dition of a carboxy terminal peptide selected from the group consisting of SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 23, or both to further en-hance the solubility of the glucagon agonist analogs.

L'invention concerne des peptides de glucagon modifiés présentant une solubilité et/ou une demi-vie améliorée, l'activité agoniste du glucagon étant toutefois conservée. Les peptides glycogènes ont été modifiés par substitution d'aminoacides natifs à l'aide et/ou par ajout d'aminoacides chargés sur la terminaison carboxy du peptide. Les agonistes de glucagon modifiés peuvent être également modifiés par pégylation, ou l'ajout d'un peptide à terminaison carboxy sélectionné parmi le groupe constitué de SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 23, ou les deux, de manière à améliorer la solubilité des analogues des agonistes de glucagon.

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