Glucagon/glp-1 receptor co-agonists

Details Glucagon/glp-1 receptor co-agonists Glucagon/glp-1 receptor co-agonists

C - Chemistry, Metallurgy

07

K

C07K 14/605 (2006.01) A61K 38/00 (2006.01) A61K 38/26 (2006.01) A61P 3/04 (2006.01) A61P 3/10 (2006.01) C07K 14/72 (2006.01)

Patent

CA 2728284

Modified glucagon peptides are disclosed having enhanced potency at the glucagon receptor relative to native glucagon. Further modification of the glucagon peptides by forming intramolecular bridges or the substitution of the terminal carboxylic acid with an amide group produces peptides exhibiting glucagon/GLP- 1 receptor co-agonist activity. The solubility and stability of these high potency glucagon analogs can be further improved by modification of the polypeptides by pegylation, acylation, alkylation, substitution of carboxy terminal amino acids, C- terminal truncation, or the addition of a carboxy terminal peptide selected from the group consisting of SEQ ID NO: 26 (GPSSGAPPPS), SEQ ID NO: 27 (KRNRNNIA) and SEQ ID NO: 28 (KRNR).

L'invention concerne des peptides de glucagon modifié présentant une puissance améliorée sur le récepteur du glucagon par rapport au glucagon de départ. Une modification supplémentaire des peptides de glucagon par formation de ponts intramoléculaires ou par substitution de l'acide carboxylique terminal par un groupe amide produit des peptides présentant une activité co-agoniste du récepteur glucagon/GLP-1. La solubilité et la stabilité des analogues de glucagon à puissance élevée peuvent être améliorées par modification des polypeptides par pégylation, acylation, alkylation, substitution des aminoacides à terminaison carboxy, par troncature du terminal C, ou l'ajout d'un peptide à terminaison carboxy sélectionné parmi le groupe constitué de SEQ ID NO: 26 (GPSSGAPPPS), SEQ ID NO: 27 (KRNRNNIA) and SEQ ID NO: 28 (KRNR).

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