Different types of strategies were developed for selective cancer therapy, such as photo-controlled drug delivery, photo-induced decaging of pro-drug, pH-mediated drug release and enzyme-induced prodrug release. These strategies endowed traditional bioactive molecules with new application. The method of enzyme-induced prodrug release has attracted intense attentions for the overexpression of alkaline phosphatases and metalloproteinases around several tumor tissues. Here, we report a new strategy that uses enzyme-induced gain of function (EIGF) to achieve selective inhibition of cancel cells. The basic concept was to screen a functional phosphorylation site, which could effectively influence the structure and activity of bioactive peptides. Upon removing the phosphorylation modification around the cancer cells with high alkaline phosphatases’ activity, the bioactive peptides could regain their conformation and function. Using melittin analogues (MelAs), which have the capacity to disrupt plasma membranes and induce cell death without selectivity, as the model peptides, we proved our EIGF concept<i> in vitro</i> and on cell level. This strategy provides new view for the design and discovery of prodrugs and cancer-targeted drugs.

Enzyme-induced gain of function strategy for selective cancer therapy

256th National Meeting (2018)

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