abstract |
Novel polypeptide derivatives having protracted profile of action. The present invention relates to a compound which comprises a therapeutic polypeptide linked to an albumin binding residue via a hydrophilic spacer. The present invention also relates to a compound which comprises a therapeutic polypeptide linked to an albumin binding residue via a hydrophilic spacer that separates the polypeptide and the albumin binding residue with a chemical moiety comprising at least 5 non-hydrogen atoms where 30-50% of these atoms are either N or O. In one embodiment of this invention the spacer is defined as —(CH 2 ) l D[(CH 2 ) n E] m (CH 2 ) p Q q -, wherein l, m and n independently are 1-20 and p is 0-10, Q is -Z-(CH 2 ) l D[(CH 2 ) n G] m (CH 2 ) p —, q is an integer in the range from 0 to 5, each D, E and G independently are selected from —O—, NR 3 —, —N(COR 4 )—, —PR 5 (O)—, and —P(OR 6 )(O)—, wherein R 3 , R 4 , R 5 , and R 6 independently represent hydrogen or C 1-6 -alky, Z is selected from —C(O)NH—, —C(O)NHCH 2 —, —OC(O)NH—, —C(O)NHCH 2 CH 2 —, —C(O)CH 2 —, —C(O)CH═CH—, —(CH 2 ) s —, —C(O)—, —C(O)O— or —NHC(O)—, wherein s is 0 or 1. |