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A recombinant immunotoxin consisting of two antibody variable domains fused to Pseudomonas exotoxin 总被引:23,自引:0,他引:23
V K Chaudhary C Queen R P Junghans T A Waldmann D J FitzGerald I Pastan 《Nature》1989,339(6223):394-397
Antibodies and growth factors have been chemically coupled to different toxins to produce cytotoxic molecules that selectively kill cells bearing appropriate antigens or receptors. Antibody-toxin conjugates (immunotoxins) produced using conventional chemical coupling techniques have several undesirable characteristics. The smallest binding unit of an antibody is an Fv fragment which consists of a light and heavy chain variable domain. Recently, active single chain Fv fragments of antibodies have been produced in Escherichia coli by attaching the light and heavy chain variable domains together with a peptide linker. Here we describe the construction and expression in E. coli of a single chain antibody toxin fusion protein, anti-Tac(Fv)-PE40, in which the variable regions of anti-Tac, a monoclonal antibody to the p55 subunit of the human interleukin-2 receptor, are joined in peptide linkage to PE40, a modified form of Pseudomonas exotoxin lacking its binding domain. Anti-Tac(Fv)-PE40 was very cytotoxic to two interleukin-2 receptor-bearing human cell lines but was not cytotoxic to receptor-negative cells. 相似文献
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Transglutaminase is essential in receptor-mediated endocytosis of alpha 2-macroglobulin and polypeptide hormones 总被引:41,自引:0,他引:41
P J Davies D R Davies A Levitzki F R Maxfield P Milhaud M C Willingham I H Pastan 《Nature》1980,283(5743):162-167
The receptor-mediated endocytosis of alpha 2-macroglobulin can be inhibited by a diverse group of chemical compounds all of which share the property of being inhibitors of one form of cellular transglutaminase. The present results strongly suggest that protein cross-linking may be essential for receptor-mediated endocytosis of some protein and polypeptide hormones. 相似文献
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Cyclic AMP regulates catabolite and transient repression in E. coli 总被引:31,自引:0,他引:31
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Expression of the product of the transforming gene (src) of RNA tumour viruses promotes growth and usually alters the adhesion, appearance and surface properties of cultured fibroblasts. The latter group of properties termed the 'morphologic phenotype' of transformed cells is largely due to diminished cell-to-substratum adhesion. The role of cyclic AMP, cell surface protein (CSP), and other factors in producing the 'morphologic phenotype' are discussed. The effects of src expression bear a striking resemblance to the action of peptide hormones such as insulin on appropriate target cells. 相似文献
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Selective killing of HIV-infected cells by recombinant human CD4-Pseudomonas exotoxin hybrid protein 总被引:40,自引:0,他引:40
V K Chaudhary T Mizukami T R Fuerst D J FitzGerald B Moss I Pastan E A Berger 《Nature》1988,335(6188):369-372
It is projected that in the absence of effective therapy, most individuals infected with human immunodeficiency virus (HIV) will develop acquired immune deficiency syndrome (AIDS) and ultimately succumb to a combination of opportunistic microbial infections, malignancies and direct pathogenic effects of the virus. Anti-viral agents, immunomodulators, and inhibitors of specific HIV functions are being tested as potential treatments to alleviate the high morbidity and mortality. An alternative therapeutic concept involves the development of cytotoxic agents that are targeted to kill HIV-infected cells. Here we describe the purification and characterization of a recombinant protein produced in Escherichia coli that contains the HIV-binding portion of the human CD4 molecule linked to active regions of Pseudomonas exotoxin A. This hybrid protein displays selective toxicity toward cells expressing the HIV envelope glycoprotein and thus represents a promising novel therapeutic agent for the treatment of AIDS. 相似文献
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Regulation of cell motility by cyclic AMP 总被引:19,自引:0,他引:19
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