What is it about?

In this work, we developed a computational approach to design small proteins that specifically recognize a protein region inside the membrane to modulate its interactions with other proteins. We used this method to block the interactions established between proteins involved in cell death regulation. By blocking these interactions that happen inside the membrane, we succeeded on making cancer-like cells sensitive to a chemotherapeutic drug.

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Why is it important?

Previous successful design of intramembrane interactions is limited. Our findings facilitate the design transmembrane interactions based only on the sequence of the target receptor. Thus, we have developed a suitable pipeline to design inhibitors against any process in which interactions within biological membranes participate.


This new approach is focused on a target that has not been explored before. We hope that this work will open a new way for the development of new therapies against cancer and other diseases.

Gerard Duart
Universitat de Valencia

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This page is a summary of: Computational design of BclxL inhibitors that target transmembrane domain interactions, Proceedings of the National Academy of Sciences, March 2023, Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.2219648120.
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