Design of toxins that can be activated by cell-specific proteases and their potential use in targeted cell killing

Protein toxins designed to eliminate specific cell types, e. g. disease-associated cells, have mainly made by linking the active domain of the toxin to a protein that only binds to certain cells. A different approach for the construction of toxins capable of killing disease-associated cells is sugge...

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Bibliographic Details
Published in:International journal of medical microbiology 2000-10, Vol.290 (4), p.471-476
Main Author: Falnes, P.Ø.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
anthrax toxin
Antigens, Bacterial
Bacterial Toxins - metabolism
Bacterial Toxins - pharmacology
Biological and medical sciences
Biotechnology
Cell Survival - drug effects
Diphtheria toxin
Diphtheria Toxin - metabolism
Diphtheria Toxin - pharmacology
Fundamental and applied biological sciences. Psychology
Health. Pharmaceutical industry
HeLa Cells
HIV protease
HIV Protease - pharmacology
Humans
Industrial applications and implications. Economical aspects
Miscellaneous
Molecular Sequence Data
N-end rule
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Summary:Protein toxins designed to eliminate specific cell types, e. g. disease-associated cells, have mainly made by linking the active domain of the toxin to a protein that only binds to certain cells. A different approach for the construction of toxins capable of killing disease-associated cells is suggested here, based on the knowledge that many of these cells express specific proteases that are not expressed in normal tissue. The construction of toxins that become activated through cleavage by the protease (HIV-1 PR) expressed by the HIV-1 virus is described. These toxins contain a signal for degradation by the N-end rule pathway, which is cleaved off by HIV-1 PR, resulting in increased toxicity. Alternative strategies for the construction of toxins that can be activated by proteases are discussed.
ISSN:1438-4221
1618-0607
DOI:10.1016/S1438-4221(00)80068-5