Polynucleotide: adenosine glycosidase activity of immunotoxins containing ribosome-inactivating proteins.
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.
Barbieri
L
L
Dipartimento di Patologia Sperimentale dell'Università degli Studi di Bologna, Via San Giacomo 14, I-40126 Bologna, Italy.barbieri@alma.unibo.it
Bolognesi
A
A
Valbonesi
P
P
Polito
L
L
Olivieri
F
F
Stirpe
F
F
D000225:Adenine / Q000378:metabolism; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D000922:Immunotoxins / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D009699:N-Glycosyl Hydrolases / Q000737:chemistry / Q000494:pharmacology*; D010940:Plant Proteins / Q000737:chemistry; D011500:Protein Synthesis Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D011506:Proteins / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits; D054788:Ribosome Inactivating Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins
D000972:Antineoplastic Agents, Phytogenic; D000922:Immunotoxins; D010940:Plant Proteins; D011500:Protein Synthesis Inhibitors; D011506:Proteins; D054789:Ribosome Inactivating Proteins, Type 1; C470296:momordin I (protein); D004247:DNA; D009699:N-Glycosyl Hydrolases; D054788:Ribosome Inactivating Proteins; D000076985:Saporins; D000225:Adenine