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 × 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.
Original language | English (US) |
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Pages (from-to) | 563-570 |
Number of pages | 8 |
Journal | Cell |
Volume | 22 |
Issue number | 2 |
DOIs | |
State | Published - 1980 |
Externally published | Yes |
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology