Institute of Organic Chemistry, Heidelberg University, Im Neuenheimer Feld 270, 69120, Heidelberg, Germany.
Centre for Advanced Materials, Im Neuenheimer Feld 225, 69120, Heidelberg, Germany.
Chembiochem. 2021 May 14;22(10):1779-1783. doi: 10.1002/cbic.202000865. Epub 2021 Mar 5.
A two-step synthesis for methionine-containing hydrophobic and/or aggregation-prone peptides is presented that takes advantage of the reversibility of methionine oxidation. The use of polar methionine sulfoxide as a building block in solid-phase peptide synthesis improves the synthesis quality and yields the crude peptide, with significantly improved solubility compared to the reduced species. This facilitates the otherwise often laborious peptide purification by high-performance liquid chromatography. The subsequent reduction proceeds quantitatively. This approach has been optimised with the methionine-rich Tar-DNA-binding protein 43 (307-347), but is also more generally applicable, as demonstrated by the syntheses of human calcitonin and two aggregation-prone peptides from the human prion protein.
本文提出了一种两步合成法，用于合成含蛋氨酸的疏水性和/或易于聚集的肽，该方法利用了蛋氨酸氧化的可逆性。在固相肽合成中使用极性蛋氨酸亚砜作为构建块可以改善合成质量，并得到粗肽，与还原态相比，其溶解度显著提高。这有助于通过高效液相色谱法进行原本通常很繁琐的肽纯化。随后的还原反应定量进行。该方法已通过富含蛋氨酸的 Tar-DNA 结合蛋白 43（307-347）进行了优化，但也具有更普遍的适用性，如人类降钙素和两种来自人类朊病毒蛋白的易于聚集的肽的合成所示。
