METHOD FOR THE SOLID-PHASE SYNTHESIS OF DUAL GLP-1 / GIP AGONISTS

Claims

The present invention provides for the use of dipeptide fragments in the solid-phase synthesis of a polypeptide compound, and a method for solid-phase synthesis of a polypeptide using dipeptide fragments, the dipeptide fragments being selected from the following structures: Gly-Gly, Ille-Aib, Tyr-Aib, Thr-αMePhe, and Glu-Gly.

1. Use of dipeptide fragments in the solid-phase synthesis of a polypeptide compound, characterized in that the dipeptide fragments are selected from the following structures: Gly-Gly, Ile-Aib, Tyr-Aib, Thr-αMePhe, and Glu-Gly, and the polypeptide compound is a compound of Formula AI (SEQ ID No. 12): H-Tyr 1 -Aib 2 -Glu 3 -Gly 4 -Thr 5 -αMePhe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Aib 11 -Ile 12 -Aib 13 -Leu 14 -Asp 15 -Lys 16 -Gln 17 -Ala 18 -Gln 19 -Ala 20 -Glu 21 -Phe 22 -Val 23 -Lys 24 -Trp 25 -Leu 26 -Leu 27 -Lys 28 -Gly 29 -Gly 30 -Pro 31 -Ser 32 -Ser 33 -Gly 34 -Ala 35 -Pro 36 -Pro 37 -Pro 38 -Ser 39 -Lys 40 -NH2 Formula AI, and has the following structure: (1), wherein optionally, at any lysine in the selected position of position 16, position 24, position 28 and position 40, the ε amino group of the side chain is chemically modified with ([2-(2-amino-ethoxy)-ethoxy]-acetyl)a-(γ-Glu)b-CO-(CH2)c-COOH,where each a is independently an integer from 0 to 5, each b is independently an integer from 0 to 5, and each c is independently an integer from 10 to 24.

9. A method for the solid-phase synthesis of a polypeptide compound using dipeptide fragments, characterized in that the polypeptide compound is a compound of Formula AI, H-Tyr 1 -Aib 2 -Glu 3 -Gly 4 -Thr 5 -αMePhe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Aib 11 -Ile 12 -Aib 13 -Leu 14 -Asp 15 -Lys 16 -Gln 17 -Ala 18 -Gln 19 -Ala 20 -Glu 21 -Phe 22 -Val 23 -Lys 24 -Trp 25 -Leu 26 -Leu 27 -Lys 28 -Gly 29 -Gly 30 -Pro 31 -Ser 32 -Ser 33 -Gly 34 -Ala 35 -Pro 36 -Pro 37 -Pro 38 -Ser 39 -Lys 40 -NH2 Formula AI (SEQ ID No. 12), and has the following structure: (1) wherein optionally, at any lysine at the selected position of position 16, position 24, position 28 and position 40, the ε amino group of the side chain is chemically modified with ([2-(2-amino-ethoxy)-ethoxy]-acetyl)a-(γ-Glu)b-CO-(CH2)c-COOH, wherein each a is independently an integer from 0 to 5, each b is independently an integer from 0 to 5,and each c is independently an integer from 10 to 24, the dipeptide fragments are selected from the following structures: Gly-Gly, Ile-Aib, Tyr-Aib, Thr-αMePhe and Glu-Gly.