A hybrid protein containing the toxic subunit of ricin and the cell-specific subunit of human chorionic gonadotropin. II. Biologic properties.

Abstract

The biologic properties of a purified hybrid protein containing the toxic subunit A of ricin and the cell-specific subunit of human chorionic gonadotropin (hCGbeta) in a disulfide conjugate is reported. The biologic activity of the hybrid has been studied by assaying inhibition of protein synthesis in rat R2C Leydig cells and mouse L-cells. The results indicate that for the A subunit to exhibit its toxic effect it must first bind to cells through receptors which are specific for the beta subunit of the hybrid. Thus, only cells with beta-type receptors are sensitive to the toxic effects, which hCG is capable of blocking, while cells which are not target cells for hCG are not subject to the toxic effects. Thus it is concluded that the disulfide conjugate may act as a functional analog of ricin toxin but with altered cell specificity. Or, alternately, the hybrid may be regarded as an analog of hCG but with drastically altered physiologic effects.