Role of single disulfide linkages in the folding and activity of scyllatoxin‐based BH3 domain mimetics |
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| Authors: | Danushka Arachchige M. Margaret Harris Zachary Coon Jacob Carlsen Justin M. Holub |
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| Affiliation: | 1. Department of Chemistry and Biochemistry, Ohio University, Athens, OH, USA;2. Edison Biotechnology Institute, Ohio University, Athens, OH, USA;3. Molecular and Cellular Biology Program, Ohio University, Athens, OH, USA |
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| Abstract: | Anti‐apoptotic Bcl‐2 proteins are implicated in pathogenic cell survival and have attracted considerable interest as therapeutic targets. We recently developed a class of synthetic peptide based on scyllatoxin (ScTx) designed to mimic the helical BH3 interaction domain of the pro‐apoptotic Bcl‐2 protein Bax. In this communication, the contribution of single disulfides in the folding and function of ScTx‐Bax peptides was investigated. We synthesized five ScTx‐Bax variants, each presenting a different combination of native disulfide linkage and evaluated their ability to directly bind Bcl‐2 in vitro. It was determined that the position of the disulfide linkage had significant implications on the structure and function of ScTx‐Bax peptides. This study underscores the importance of structural dynamics in BH3:Bcl‐2 interactions and further validates ScTx‐based ligands as potential modulators of anti‐apoptotic Bcl‐2 function. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd. |
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| Keywords: | BH3 domain mimetic anti‐apoptotic Bcl‐2 proteins scyllatoxin disulfide linkage apoptosis ligand binding |
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