Copper chelates as probes of biological systems: stable copper complexes with a macrocyclic bifunctional chelating agent.

Monoclonal antibodies tagged with chelated metal ions have numerous potential applications. Here we report the synthesis of a new "bifunctional" metal chelator, 6(p-bromoacetamidobenzyl)-1,4,8,11-tetraazacyclotetradecane- N,N',N",N"' -tetraacetic acid, which can be covalently attached to proteins and which binds copper stably in human serum under physiological conditions. In contrast, other reagents based on ethylenediaminetetraacetic acid or diethylenetriaminepentaacetic acid rapidly lose copper to serum albumin under the same conditions.