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SELF-POTENTIATION OF LIGAND-TOXIN CONJUGATES CONTAINING RICIN-A CHAIN FUSED WITH VIRAL STRUCTURES
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UNSPECIFIED (1995) SELF-POTENTIATION OF LIGAND-TOXIN CONJUGATES CONTAINING RICIN-A CHAIN FUSED WITH VIRAL STRUCTURES. JOURNAL OF BIOLOGICAL CHEMISTRY, 270 (40). pp. 23345-23351. ISSN 0021-9258.
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Abstract
A chimeric protein was obtained by fusing together the ricin toxin A chain (RTA) gene and a DNA fragment encoding the N terminus of protein G of the vesicular stomatitis virus. Chimeric RTA (cRTA) retained full enzymic activity in a cell-free assay, but was 10-fold less toxic against human leukemic cells than either native RTA (nRTA) or unmodified recombinant RTA (rRTA). However, conjugates made with cRTA and human transferrin (Tfn) showed 10-20 fold greater cell killing efficacy than Tfn-nRTA or Tfn-rRTA conjugates despite equivalent binding of the three conjugates to target tumor cells. As a consequence, by fusion of the KFT25 peptide to the RTA sequence, the specificity factor (i.e. the ratio between nonspecific and specific cytotoxicity) of Tfn-cRTA was increased 90-240 times with respect to those of Tfn-nRTA and Tfn-rRTA. cRTA interacted with phospholipid vesicles with 15-fold faster kinetics than nRTA at acidic pH. Taken together, our results suggest that the ability of vesicular stomatitis virus protein G to interact with cell membranes can be transferred to RTA to facilitate its translocation to the cell cytosol. Our strategy may serve as a general approach for potentiating the cytotoxic efficacy of antitumor immunotoxins.
Item Type: | Journal Article | ||||
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Subjects: | Q Science > QD Chemistry | ||||
Journal or Publication Title: | JOURNAL OF BIOLOGICAL CHEMISTRY | ||||
Publisher: | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | ||||
ISSN: | 0021-9258 | ||||
Official Date: | 6 October 1995 | ||||
Dates: |
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Volume: | 270 | ||||
Number: | 40 | ||||
Number of Pages: | 7 | ||||
Page Range: | pp. 23345-23351 | ||||
Publication Status: | Published |
Data sourced from Thomson Reuters' Web of Knowledge
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