Interaction of a doxorubicin-transferrin conjugate with isolated transferrin receptors

It is shown that transferrin-doxorubicin conjugates bind to isolated transferrin receptors. The receptors were isolated from human full-term placenta by solubilization of trophoblast plasma membranes with the nonionic detergent C12E8 and then by affinity chromatography on a diferric transferrin-coupled Sepharose CL-4B column. The binding affinity of such conjugate was similar to that of transferrin. Dissociation of conjugate from the isolated receptor occurred with time-dependent kinetics similar to those of transferrin when the experimental conditions mimicking the physiological steps of transferrin recycling were consecutively applied. These results support the idea that a) binding of such conjugates is primarily governed by the interaction between the transferrin part of the conjugates and the transferrin receptor, and b) it is not the transferrin receptor itself which participates in the putative secondary interaction between the receptor-bound conjugates and plasma membrane.