New peptide derivative heterobifunctional coupling agents containing aminooxy and maleimide groups, used for coupling aldehyde or ketone compound with thiol, especially for preparing diagnostic agents

摘要

Heterobifunctional functional coupling agents (I), comprising peptide derivatives containing at least one 8-amino-3,6-dioxa-octanoic acid unit and aminooxy and maleimide functional groups, are new. Heterobifunctional functional coupling agents of formula (I), comprising peptide derivatives containing at least one 8-amino-3,6-dioxa-octanoic acid unit and aminooxy and maleimide functional groups, are new. W = NH-(CH2)2O(CH2)2-OCH2CO; A = (W')p-CO-(CH2)u-Mal (a), (W')p-CO-CH-((CH2)rNH-(W')p-CO-(CH2)u-Mal)2 (b) or (W')p-CO-CH(-(CH2)rNH-(W')p-CO-CH(-(CH2)r-NH-(W')p-CO-(CH2)u-Mal)2)-(CH2)q-NH-(W')p-CH(-(CH2)r-NH-(W')p-CO-(CH2)u-Mal)2 (c); D = group (a), (b), (c) or CO-(CH2)u-Mal (d); Mal = maleimide; Y = group terminated by CONH2 and inert with respect to the remainder of the molecule; W' = COCH2O-(CH2)2O(CH2)2-NH; n = 0-3; m, o = 0-3; p = 1-4; q = 0-3; r = 2-5; s = 0 or 1; t = 1-7, and u = 2-10. Independent claims are also included for: (1) new activated intermediates (II) comprising (I) and a molecule (II') having at least one surface aldehyde and/or ketone function before conjugation; (2) new activated intermediates (III) comprising (I) and 1-8 (preferably 1-4) molecule(s) (III') having at least one surface thiol function before conjugation; and (3) new conjugates (IV) comprising (I) bonded to (II') and to 1-8 molecule(s) (III').