A crucial step in preclinical drug development is the confirmation of the novel therapeutic molecule's specific binding to the targeted protein. Transmembrane proteins (TPs) like ion channels, transporters, or receptors provide many targets for cancer and other diseases. They are complex, making producing those proteins in suitable amounts much more challenging than their soluble counterparts. This results in a bottleneck in the drug discovery workflow.
New approaches to aid drug development include full-length transmembrane protein platforms, which offer purified, high-quality TPs as ready-to-use items for drug-target interaction analyses.
Image Credit: ACROBiosystems
Meet the claudin family: Gatekeepers in cancer
The Claudin protein family provides examples of TP drug targets. This group of TPs has a core role in tight junctions, gatekeeping structures responsible for regulating the flow of ions and water between endothelial and epithelial cells.
In addition to other functions, tight junctions support tissue structure integrity, which prevents cancer cells from migrating through the endothelial barrier and entering the bloodstream. Recently, studies have indicated that abnormal expression rates of Claudin protein family members are related to tumor growth and metastasis, making them relevant therapeutic targets and factors in cancer prognosis.
Claudins contain four transmembrane-spanning domains with peptide loops on the membrane's exterior. Combined, those loops form three-dimensional structures, or epitopes, targeted by diagnostic or therapeutic antibodies.
“Producing only the isolated soluble loops of the Claudin proteins would be fast and easy. However, we know that because the individual peptides do not interact correctly, the three-dimensional structure required for reliable antibody screening does not form. But when we express Claudins as full-length TPs, the transmembrane domains hold the external loops in the correct position,” says Dr. Spencer Chiang, ACROBiosystems’ Communication Manager.
Interaction studies using therapeutic molecules and antibodies can only present meaningful results when the target is offered in its biologically relevant conformation. This calls for methods that allow the production of correctly folded, active, full-length TPs. Establishing these methods remains challenging while varying between individual protein targets.
About ACROBiosystems
ACROBiosystems is a cornerstone enterprise of the pharmaceutical and biotechnology industries. Their mission is to help overcome challenges with innovative tools and solutions from discovery to the clinic. They supply life science tools designed to be used in discovery research and scalable to the clinical phase and beyond. By consistently adapting to new regulatory challenges and guidelines, ACROBiosystems delivers solutions, whether it comes through recombinant proteins, antibodies, assay kits, GMP-grade reagents, or custom services. ACROBiosystems empower scientists and engineers dedicated towards innovation to simplify and accelerate the development of new, better, and more affordable medicine.
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