BIFUNCTIONAL AROMATIC ISOCYANATES OR ISOTHIOCYANATES AND METHOD FOR LINKING AMINE LIGANDS UTILIZING THE SAME

摘要

A selective bifunctional sequential linker has the formula P PY═C═N--Q--A--C(O)--ZPPwherein Q is a homoaromatic or heteroaromatic ring system; A is a single bond or an unsubstituted or substituted divalent C.sub.1-30 bridging group; Y is O or S; and Z is Cl, Br, I, N.sub.3, 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 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.P PThe 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.