Ribosome-Inactivating Protein–Small Molecule Conjugates can Selectively Inhibit Target-Specific Tumor Cell Growth

Cell-targeting conjugates of Saporin 6, a ribosome inactivating protein (RIP), were prepared using the Saporin Ala 157 Cys mutant, a small molecule inhibitor of integrin αvβ3, and a potent cytotoxin, auristatin F (AF). The conjugates selectively and potently inhibited proliferation of tumor cells expressing the target integrins. We anticipate that the small molecule-RIP bioconjugate approach can be broadly applied using other small molecule drugs. Cell-targeting conjugates of Saporin 6, prepared using a small molecule inhibitor of integrins avb3 and avb5 and Saporin A157C mutant, selectively and potently inhibited proliferation of tumor cells expressing the target integrins.