| abstract |
The invention relates to a derivative of a GLP-1 analogue, which analogue comprises a first K residue at a position corresponding to position 37 of GLP-1(7-37) (SEQ ID NO: 1), a second K residue at a position corresponding to position 26 of GLP-1(7-37), and a maximum of ten amino acid modifications as compared to GLP-1(7-37), wherein the first K residue is designated K 37 , and the second K residue is designated K 26 , which derivative comprises two albumin binding moieties attached to K 26 and K 37 , respectively, wherein the albumin binding moiety comprises a protracting moiety selected from: n HOOC—(CH 2 ) x —CO—* Chem. 1:n n HOOC—C 6 H 4 —O—(CH 2 ) y —CO—* Chem. 2:n n R 1 —C 6 H 4 —(CH 2 ) z —CO—* Chem. 3:n n HOOC—C 4 SH 2 —(CH 2 ) w —CO—* Chem. 4:n n in which x is an integer in the range of 6-18, y is an integer in the range of 3-17, z is an integer in the range of 1-5, R 1 is a group having a molar mass not higher than 150 Da, and w is an integer in the range of 6-18; with the proviso that when the protracting moiety is Chem. 1, the albumin binding moiety further comprises a linker of formula Chem. 5: *—NH—(CH 2 ) 2 —(O—(CH 2 ) 2 ) k —O—(CH 2 ) n —CO—*, wherein k is an integer in the range of 1-5, and n is an integer in the range of 1-5; or a pharmaceutically acceptable salt, amide, or ester thereof. n The invention also relates to the pharmaceutical use thereof, for example in the treatment and/or prevention of all forms of diabetes and related diseases, as well as to corresponding novel peptides and side chain intermediates. The derivatives are suitable for oral administration. |