Polynucleotide: adenosine glycosidase activity of immunotoxins containing ribosome-inactivating proteins

Abstract

Polynucleotide:adenosine glycosidases (rRNA N-glycosidases, EC 3.2.2.22, more commonly known as ribosome-inactivating proteins, RIP) are a numerous family of plant and bacterial enzymes, shown to release also adenine from DNA in vitro. They are well suited for the preparation of specifically toxic conjugates with several carriers, including monoclonal antibodies (immunotoxins). Here we show that (i) immunotoxins containing various PNAG (dianthin, gelonin, momordin I, PAP-S, PDS-2, ricin A-chain, saporin-L1, saporin-S6) all act on DNA; (ii) activity on DNA in vitro is less compromised by disulphide linkage to antibody than is inhibition of cell-free protein translation; and (iii) specific cytotoxicity of immunotoxin does not correlate with substrate specificity.