Conjugation of bleomycin with concanavalin A or immunoglobulin G increases its ability to destroy cell membranes

Abstract

Hybrid molecules consisting of an address peptide and an active oxygen-generating fragment may be used for selective destruction of cells. We tested the possibility of using the antibiotic bleomycin (BLM) as an active oxygen-generating fragment of such a molecule. It was found that bleomycin can induce destruction of cell membranes. BLM-mediated cell destruction was inhibited by addition of catalase, superoxide dismutase, and OH. scavangers (mannitol and ethanol), suggesting that hydroxy radical is involved in the process. BLM can induce membrane impairment at the expense of electrons supplied by NADPH-cytochrome P450 reductase. Covalent binding of BLM to an address fragment (concanavalin A, immunoglobulin G) increases the ability of BLM to destroy erythrocyte membranes. The data obtained lead to the conclusion that BLM can be used as an active oxygen-generating fragment of a proposed cell-destroying hybrid molecule.