Calce Enrica, Vitale Rosa Maria, Scaloni Andrea, Amodeo Pietro, De Luca Stefania
Institute of Biostructures and Bioimaging, National Research Council, 80138, Naples, Italy.
Amino Acids. 2015 Aug;47(8):1507-15. doi: 10.1007/s00726-015-1983-4. Epub 2015 Apr 22.
Among the available protocols, chemically driven approaches to oxidize cysteine may not be required for molecules that, under the native-like conditions, naturally fold in conformations ensuring an effective pairing of the right disulfide bridge pattern. In this contest, we successfully prepared the distinctin, a natural heterodimeric peptide, and some synthetic cyclic peptides that are inhibitors of the CXCR4 receptor. In the first case, the air oxidation reaction allowed to connect two peptide chains via disulfide bridge, while in the second case allowed the cyclization of rationally designed peptides by an intramolecular disulfide bridge. Computational approaches helped to either drive de-novo design or suggest structural modifications and optimal oxidization protocols for disulfide-containing molecules. They are able to both predict and to rationalize the propensity of molecules to spontaneously fold in suitable conformations to achieve the right disulfide bridges.
在现有的方案中，对于那些在类似天然条件下能自然折叠成确保正确二硫键模式有效配对构象的分子，可能不需要采用化学驱动的方法来氧化半胱氨酸。在这种情况下，我们成功制备了天然异二聚体肽distinctin以及一些作为CXCR4受体抑制剂的合成环肽。在第一种情况下，空气氧化反应使得两条肽链通过二硫键连接，而在第二种情况下，则通过分子内二硫键实现了合理设计肽的环化。计算方法有助于推动从头设计，或为含二硫键分子提出结构修饰和最佳氧化方案。它们既能预测又能合理解释分子自发折叠成合适构象以形成正确二硫键的倾向。
