Biologic activity of daunorubicin linked to proteins via the methylketone side chain.

New daunorubicin-protein conjugates were prepared by covalently linking the antitumor drug to various test proteins via its methylketone side chain. Attachment of daunorubicin to proteins was achieved by nucleophylic substitution reaction of the 14-bromo derivative of the drug, under mild coupling conditions. In contrast to conventional methods, this procedure did not involve reaction or modification of the amino sugar. As expected, the covalent linkage of the drug was generally associated with an appreciable reduction in the drug cytotoxicity to HeLa cells in vitro. The possible advantages of this method for coupling to specific protein carriers are discussed.