- GND
- 1297139445
- LSF ID
- 60535
- ORCID
- 0000-0002-3762-4832
- Sonstiges
- der Hochschule zugeordnete*r Autor*in
- GND
- 1193736498
- LSF ID
- 60536
- Sonstiges
- der Hochschule zugeordnete*r Autor*in
- LSF ID
- 59056
- Sonstiges
- der Hochschule zugeordnete*r Autor*in
- LSF ID
- 60015
- Sonstiges
- der Hochschule zugeordnete*r Autor*in
- LSF ID
- 59441
- ORCID
- 0000-0002-0793-0249
- Sonstiges
- der Hochschule zugeordnete*r Autor*in
- GND
- 1013479785
- LSF ID
- 57758
- ORCID
- 0000-0002-9612-2306
- Sonstiges
- der Hochschule zugeordnete*r Autor*in
- LSF ID
- 51606
- ORCID
- 0000-0003-4321-0924
- Sonstiges
- der Hochschule zugeordnete*r Autor*in
Abstract in Englisch:
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 effects in different tumor cell lines, resulting in comparable EC₅₀ values (∼40–70 μM). Of note, in higher concentrations, 2GC also interfered with Taspase1’s proteolytic activity. We thus believe to set the stage for a novel class of Taspase1 inhibitors targeting a pivotal protein-protein interaction prerequisite for its cancer-associated proteolytic function.