Inhibitory Potential and Binding Thermodynamics of Scyllatoxin-Based BH3 Domain Mimetics Targeting Repressor BCL2 Proteins.

The B-cell lymphoma 2 (BCL2) proteins are a class of apoptosis regulators that control the release of apoptogenic factors from mitochondria. Under normal physiological conditions, apoptosis is inhibited through the actions of anti-apoptotic (repressor) BCL2 proteins that bind semi-indiscriminately to the helical BH3 domains of pro-apoptotic (effector) BCL2 proteins. In this work, we developed a series of BH3 domain mimetics by grafting residues from the effector BCL2 protein Bax onto the α-helix of scyllatoxin (ScTx).