A Bivalent Supramolecular GCP Ligand Enables Blocking of the Taspase1/Importin α Interaction.

ABSTRACT: Taspase1 is a unique protease not only pivotal for embryonic development but also implicated in leukemia as well as solid tumors. As such, it is a promising target in cancer therapy, although only a limited number of Taspase1 inhibitors lacking general applicability are currently available. Here we present a bivalent guanidiniocarbonyl-pyrrole (GCP)-containing supramolecular ligand that is capable of disrupting the essential interaction between Taspase1 and its cognate import receptor Importin α in a concentration-dependent manner in vitro with an IC₅₀ of 35 μM. Here, size of the bivalent vs the monovalent construct as well as its derivation with an aromatic cbz-group arose as critical determinants for efficient interference of 2GC. This was also evident when we investigated the

SUBMITTER: Hoing A 

PROVIDER: S-EPMC9298320 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature