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 -(CH2)lD[(CH2)nE]m(CH2)pQq-, wherein l, m and n independently are 1-20 and p is 0-10, Q is -Z-(CH2)lD[(CH2)nG]m(CH2)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 C1-6-alky, Z is selected from -C(O)NH-, -C(O)NHCH2-, -OC(O)NH-, -C(O)NHCH2CH2-, -C(O)CH2-, -C(O)CH=CH-, -(CH2)s-, -C(O)-, -C(O)O- or -NHC(O)-, wherein s is 0 or 1.