Polynucleotide: Adenosine Glycosidase Activity of Immunotoxins Containing Ribosome-Inactivating Proteins

AbstractPolynucleotide: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...

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Bibliographic Details
Published in:Journal of drug targeting 2000, Vol.8 (5), p.281-288
Main Authors: Barbieri, L., Bolognesi, A., Valbonesi, P., Polito, L., Olivieri, F., Stirpe, F.
Format: Article
Language:English
Subjects:
Adenine - metabolism
Animals
Antineoplastic Agents, Phytogenic - chemistry
Antineoplastic Agents, Phytogenic - pharmacology
Biological and medical sciences
DNA - drug effects
DNA - metabolism
Dose-Response Relationship, Drug
Humans
immunotoxins
Immunotoxins - chemistry
Immunotoxins - pharmacology
Medical sciences
Mice
Miscellaneous
N-Glycosyl Hydrolases - chemistry
N-Glycosyl Hydrolases - pharmacology
Plant Proteins - chemistry
polynucleotide:adenosine glycosidase
polynucleotide:adenosine glycosidase (PNAG)
Protein Synthesis Inhibitors - chemistry
Protein Synthesis Inhibitors - pharmacology
Proteins - drug effects
Proteins - metabolism
Rabbits
Ribosome Inactivating Proteins
Ribosome Inactivating Proteins, Type 1
Ribosome-inactivating protein
Toxicology
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Summary:AbstractPolynucleotide: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.
ISSN:1061-186X
1029-2330
DOI:10.3109/10611860008997906