S. Sharma et al., Comparative studies on kinetics of inhibition of protein synthesis in intact cells by ricin and conjugate of ricin B-chain with momordin, MOL C BIOCH, 200(1-2), 1999, pp. 133-141
Ribosome inactivating proteins from plants have been widely used for the pr
eparation of immunotoxins and hormonotoxins, which have potential applicati
on in the therapy of diseases such as cancer. However, these hybrid toxins
have been found to be less cytotoxic than native ribosome inactivating prot
eins. Therefore, it is important to understand the factors that control the
intrinsic toxicity of RIPs and the hybrid toxins prepared using them. Here
, a hybrid toxin has been prepared by coupling ricin B-chain to momordin an
d the cytotoxicity of this hybrid toxin has been compared to that observed
in case of native ricin. In the two cell types used here, thymocytes and ma
crophages, the conjugate was found to be about 40 fold less toxic than nati
ve ricin. Kinetics of inhibition of protein synthesis showed that prior to
onset of inhibition the conjugate exhibits a longer lag phase than native r
icin. The rates of inhibition of protein synthesis by the conjugate were al
so found to be slower than ricin. Analysis of the results suggests that in
addition to cell surface binding, the B-chain of ricin facilitates another
step in the transmembrane translocation of ricin A-chain to the cytosol.