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PMID: 10393896 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A dimeric mutant of human pancreatic ribonuclease with selective cytotoxicity toward malignant cells.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 96 ·No. 14 ·1999-07-06 ·Pages 7768-73

Piccoli R, Di Gaetano S, De Lorenzo C, Grauso M, Monaco C, Spalletti-Cernia D, Laccetti P, Cinátl J, Matousek J, D'Alessio G

Abstract

Monomeric human pancreatic RNase, devoid of any biological activity other than its RNA degrading ability, was engineered into a dimeric protein with a cytotoxic action on mouse and human tumor cells, but lacking any appreciable toxicity on mouse and human normal cells. This dimeric variant of human pancreas RNase selectively sensitizes to apoptotic death cells derived from a human thyroid tumor. Because of its selectivity for tumor cells, and because of its human origin, this protein represents a potentially very attractive, novel tool for anticancer therapy.

MeSH Terms
3T3 Cells Amino Acid Sequence Animals Antineoplastic Agents/toxicity Apoptosis/drug effects Cattle Cell Survival/drug effects Cell Transformation, Neoplastic Dimerization Drug Screening Assays, Antitumor Humans Male Mice Molecular Sequence Data Mutagenesis, Site-Directed Recombinant Proteins/biosynthesis,chemistry,toxicity Ribonuclease, Pancreatic/chemistry,genetics,toxicity Ribonucleases/chemistry Seminal Vesicles/enzymology Sequence Alignment Sequence Homology, Amino Acid Thyroid Neoplasms Tumor Cells, Cultured
Chemicals
Antineoplastic Agents Recombinant Proteins Ribonucleases Ribonuclease, Pancreatic
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Piccoli R
Department of Organic and Biological Chemistry, University of Naples Federico II, Via Mezzocannone 16, 80134 Naples, Italy.
Di Gaetano S
De Lorenzo C
Grauso M
Monaco C
Spalletti-Cernia D
Laccetti P
Cinátl J
Matousek J
D'Alessio G
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.96.14.7768
Published
1999-07-06
Pages
7768-73
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC22136
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.96.14.7768 PMC Full Text View journal details
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