CONFORMATIONALLY CONSTRAINED GLUCAGON ANALOGUES AND THEIR USE IN GLUCAGON-SINGLE CHAIN INSULIN FUSION PROTEINS
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Apr 11, 2024
app pub date -
Feb 9, 2022
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Feb 9, 2021
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Abstract
A glucagon analogue containing a lactam bridge between a Lysine introduced at position 13 and a Glutamic Acid introduced at position 17, optionally including C-terminal extensions and optionally including a second side-chain/side-chain staple beginning at or C-terminal to residue 20. The second staple may also be an (i, i+4) lactam bridge, an (i, i+3) disulfide bridge between D-Cysteine and L-Cysteine or an (i, i+7) disulfide bridge between L-Cysteine and L-Cysteine. A fusion protein containing an N-terminal lactam-stabilized glucagon analogue as above and a C-terminal single-chain insulin (SCI) analogue wherein the C domain of the SCI contains 4-11 residues is also disclosed herein. A method of treating a patient with diabetes mellitus comprises the subcutaneous, intraperitoneal, or oral administration of a physiologically effective amount of the glucagon analogue or glucagon-SCI fusion protein is also provided.
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