Department of Medicinal Chemistry, University of Utah, Salt Lake City, UT 84108, USA.
J Pept Sci. 2011 Jan;17(1):1-7. doi: 10.1002/psc.1283.
The oxidative folding of small, cysteine-rich peptides to selectively achieve the native disulfide bond connectivities is critical for discovery and structure-function studies of many bioactive peptides. As the propensity to acquire the native conformation greatly depends on the peptide sequence, numerous empirical oxidation methods are employed. The context-dependent optimization of these methods has thus far precluded a generalized oxidative folding protocol, in particular for peptides containing more than two disulfides. Herein, we compare the efficacy of optimized solution-phase and polymer-supported oxidation methods using three disulfide-bridged conotoxins, namely µ-SIIIA, µ-KIIIA and ω-GVIA. The use of diselenide bridges as proxies for disulfide bridges is also evaluated. We propose the ClearOx-assisted oxidation of selenopeptides as a fairly generalized oxidative folding protocol.
对于许多生物活性肽的发现和结构功能研究，选择性地实现天然二硫键连接的小、富含半胱氨酸的肽的氧化折叠是至关重要的。由于获得天然构象的倾向在很大程度上取决于肽序列，因此采用了许多经验性的氧化方法。迄今为止，这些方法的上下文相关优化排除了一般化的氧化折叠方案，特别是对于含有两个以上二硫键的肽。在此，我们使用三种二硫键桥接的 conotoxin（即 µ-SIIIA、µ-KIIIA 和 ω-GVIA）比较了优化的溶液相和聚合物支持的氧化方法的效果。我们还评估了使用二硒键作为二硫键的替代物。我们提出使用 ClearOx 辅助氧化硒代肽作为一个相当通用的氧化折叠方案。
