SMI-Ribosome inactivating protein conjugates selectively inhibit tumor cell growth

Abstract

Cell-targeting conjugates of Saporin 6, a ribosome inactivating protein (RIP), were prepared using the Saporin Ala 157 Cys mutant, a small molecule inhibitor (SMI) of integrins α_vβ₃/α_vβ₅, 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.