Design, Construction, and Intracellular Activation of an Intramolecularly Self‐Silenced Signal Transduction Inhibitor

Abstract

Ricin, diphtheria toxin, and other cytotoxic proteins are two-component systems which contain a carrier protein that biochemically silences the activity of the appended “warhead” protein until it is delivered into the cell. A cell-penetrating peptide (CPP) has been used in an analogous fashion (see picture) to suppress the activity of a PTP1B inhibitor that becomes activated by cleavage of the disulfide bridge upon cellular entry.