Instructed-assembly (iAssembly or iA) refers to the formation of ordered superstructures of molecules as the consequence of at least one trigger event (e.g., a reaction or a ligand-receptor interaction). Here we discuss iA of an isopeptide, which consisting of DYKDDDDK (Flag, a substrate of enterokinase (ENTK)) as the branch and a phenylalanine rich short peptide as the backbone. The isopeptides form micelles, which, upon the cleavage of the Flag catalyzed by ENTK, turn into a gel made of nanofibers. Entering cells mainly via clathrin mediated endocytosis, the isopeptide micelles interact with the mitochondria having ENTK and high membrane potential. The mitochondrial ENTK cleaves the Flag of the isopeptides, thus turning the micelles to nanofibers on the mitochondria. Mixing the isopeptides with cargos (drugs, proteins, and genes) delivers the cargos into mitochondria. For the cells without mitochondrial ENTK, the delivery hardly occurs at mitochondria. This work provides a new way to target organelles and may offer a new perspective to understanding cell specific endogenous trafficking.

Instructed-assembly of isopeptides

2019 Spring National Meeting

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