| abstract |
A selective bifunctional sequential linker has the formulaY=C=N-Q-A-C(O)-Zwherein Q is a homoaromatic or heteroaromatic ring system; A is a single bond or an unsubstituted or substituted divalent C<sub>1-30</sub> bridging group; Y is O or S; and Z is Cl, Br, I, N₃, N-succinimidyloxy, imidazolyl, 1-benzotriazolyloxy, OAr where Ar is an electron-deficient activating aryl group, or OC(O)R where R is -A-Q-N=C=Y or C<sub>4-20</sub> tertiary-alkyl. A method for activating an amine function towards reaction with a second amine involves reacting the amine with the foregoing linker. The resultant isocyanate or isothiocyanate derivative can then be reacted with a second amine to form a urea or thiourea conjugate.The linker is useful for producing conjugates of ligands with amine-containing polymers and/or proteins, especially for forming antibody conjugates with chelators, drugs, enzymes, detectable labels and the like. |