Abstract |
We have prepared a 2-pyridyl-dithiopropionate derivative of epidermal growth factor ( EGF) and conjugated the derivative by disulfide interchange to the A chain of ricin (RTA) or to fragment A of diphtheria toxin (DTA). The EGF-RTA conjugate was toxic to 3T3 cells at concentrations (10(-9)--10(-11) M) similar to those at which EGF exerts its biological activity and within an order of magnitude of the toxicity of ricin. Ricin A chain alone only exerted toxic effects at concentrations (10(-6)--10(-7) M) three to four orders of magnitude higher than required for the activity of the EGF-RTA conjugate or ricin. An unconjugated mixture of RTA and EGF had no greater effect than RTA alone. Toxicity of the EGF-RTA conjugate on 3T3 cells was competed by EGF and was blocked by antibodies to RTA, but not by lactose or antibodies to the ricin B chain (RTB). In contrast to the EGF-RTA conjugate, the EGF-DTA conjugate proved virtually nontoxic at concentrations as high as 3 X 10(-8) M. Control experiments showed that the EGF-DTA conjugate retained EGF receptor binding activity; the DTA moiety of the hybrid retained ADP-ribosyltransferase activity; and the disulfide bridge linking DTA to EGF was readily reducible.
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Authors | D B Cawley, H R Herschman, D G Gilliland, R J Collier |
Journal | Cell
(Cell)
Vol. 22
Issue 2 Pt 2
Pg. 563-70
(Nov 1980)
ISSN: 0092-8674 [Print] United States |
PMID | 6256086
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Diphtheria Toxin
- Peptides
- Receptors, Cell Surface
- Epidermal Growth Factor
- Chloroquine
- Ricin
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Topics |
- Animals
- Cells, Cultured
- Chloroquine
(pharmacology)
- Diphtheria Toxin
(toxicity)
- Endocytosis
- Epidermal Growth Factor
- Mice
- Peptides
- Protein Biosynthesis
(drug effects)
- Receptors, Cell Surface
(metabolism)
- Ricin
(toxicity)
- Structure-Activity Relationship
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