Galanis Athanassios S, Albericio Fernando, Grøtli Morten
Department of Chemistry, Medicinal Chemistry, University of Göteborg, SE-41296 Göteborg, Sweden.
Biopolymers. 2009;92(1):23-34. doi: 10.1002/bip.21116.
A novel enhanced microwave-assisted disulfide bridge formation method has been developed. To optimize the synthesis of the biologically important bicyclic peptide alpha-conotoxin MII (alpha-CtxMII), several cyclization methods have been tested and are discussed herein. By using m.w.-assisted heating, we achieved high yields for the first loop cyclization of alpha-CtxMII on-bead. This method has the advantage of avoiding intermolecular by-products during the cyclization step. Furthermore, the method gives higher yields compared with the common on-bead cyclization methods. The second disulfide bridge of alpha-CtxMII was formed using a simple oxidation method after the cleavage of the intermediate monocyclic peptide from the resin. This method has the potential to be efficient for the synthesis of other disulfide rich biologically important peptides.
一种新型的增强型微波辅助二硫键形成方法已被开发出来。为了优化具有生物学重要性的双环肽α-芋螺毒素MII（α-CtxMII）的合成，已经测试了几种环化方法，并在此进行讨论。通过使用微波辅助加热，我们在珠子上实现了α-CtxMII第一个环的环化高产率。该方法具有在环化步骤中避免分子间副产物的优点。此外，与常见的珠子上环化方法相比，该方法产率更高。在将中间的单环肽从树脂上裂解后，使用简单的氧化方法形成了α-CtxMII的第二个二硫键。该方法有可能高效地合成其他富含二硫键的具有生物学重要性的肽。
