Synthesis of Novel Heterobifunctional Isocyanato Cross‐Linkers and Their Applications for the Preparation of 10‐Hydroxycamptothecin and SN‐38 Conjugates with Melanotransferrin P97

Abstract Novel heterobifunctional cross‐linkers with an isocyanato group, a protected carboxylic group, and a linear chain spacer are synthesized in high yield by coupling monofunctionalized PEG with 1,6‐diisocyanatohexane. The isocyanato groups of those linkers are highly reactive and are efficient reagents to couple with the hydroxy groups of 10‐hydroxycamptothecin and SN‐38 under mild conditions to give a useful precursor for the synthesis of their bioconjugates with proteins such as melanotransferrin p97. Keywords: bioconjugateheterobifuncational cross‐linker10‐hydroxycamptothecinisocyanatoSN‐38