Epidermal growth factor-toxin A chain conjugates: EGF-ricin A is a potent toxin while EGF-diphtheria fragment A is nontoxic

Daniel Cawley, H. R. Herschman, D. G. Gilliland, R. J. Collier

Research output: Chapter in Book/Report/Conference proceedingChapter

104 Citations (Scopus)

Abstract

We have prepared a 2-pyridyl-dithiopropionate derivative of epidermal growth factor (EGF) and conjugated the derivative by disulfide 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 (10-9-10-11M) 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 (10-6-10-7M) 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.

Original languageEnglish (US)
Title of host publicationCell
Pages563-570
Number of pages8
Volume22
Edition2 II
StatePublished - 1980
Externally publishedYes

Fingerprint

Ricin
Diphtheria
Epidermal Growth Factor
Diphtheria Toxin
Immunotoxins
3T3 Cells
Poisons
Disulfides
ADP Ribose Transferases
Antibodies
Lactose
Epidermal Growth Factor Receptor

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Cawley, D., Herschman, H. R., Gilliland, D. G., & Collier, R. J. (1980). Epidermal growth factor-toxin A chain conjugates: EGF-ricin A is a potent toxin while EGF-diphtheria fragment A is nontoxic. In Cell (2 II ed., Vol. 22, pp. 563-570)

Epidermal growth factor-toxin A chain conjugates : EGF-ricin A is a potent toxin while EGF-diphtheria fragment A is nontoxic. / Cawley, Daniel; Herschman, H. R.; Gilliland, D. G.; Collier, R. J.

Cell. Vol. 22 2 II. ed. 1980. p. 563-570.

Research output: Chapter in Book/Report/Conference proceedingChapter

Cawley, D, Herschman, HR, Gilliland, DG & Collier, RJ 1980, Epidermal growth factor-toxin A chain conjugates: EGF-ricin A is a potent toxin while EGF-diphtheria fragment A is nontoxic. in Cell. 2 II edn, vol. 22, pp. 563-570.
Cawley D, Herschman HR, Gilliland DG, Collier RJ. Epidermal growth factor-toxin A chain conjugates: EGF-ricin A is a potent toxin while EGF-diphtheria fragment A is nontoxic. In Cell. 2 II ed. Vol. 22. 1980. p. 563-570
Cawley, Daniel ; Herschman, H. R. ; Gilliland, D. G. ; Collier, R. J. / Epidermal growth factor-toxin A chain conjugates : EGF-ricin A is a potent toxin while EGF-diphtheria fragment A is nontoxic. Cell. Vol. 22 2 II. ed. 1980. pp. 563-570
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AB - We have prepared a 2-pyridyl-dithiopropionate derivative of epidermal growth factor (EGF) and conjugated the derivative by disulfide 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 (10-9-10-11M) 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 (10-6-10-7M) 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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