Role of single disulfide linkages in the folding and activity of scyllatoxin-based BH3 domain mimetics
| Autor: | Jacob Carlsen, Justin M. Holub, Zachary Coon, Danushka Arachchige, M. Margaret Harris |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Pharmacology chemistry.chemical_classification Chemistry Stereochemistry Disulfide Linkage Organic Chemistry Disulfide bond Peptide General Medicine Computational biology Biochemistry In vitro Folding (chemistry) 03 medical and health sciences 030104 developmental biology Structural Biology Drug Discovery Scyllatoxin Molecular Medicine Molecular Biology Function (biology) Cell survival |
| Zdroj: | Journal of Peptide Science. 23:367-373 |
| ISSN: | 1075-2617 |
| DOI: | 10.1002/psc.2999 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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