Reasonable design and construction of functionalized materials are of great importance for the enrichment of global phosphopeptides. In this work, Ti⁴⁺ functionalized hydrophilic covalent organic frameworks by introducing glutathione (GSH) and 2,3,4-trihydroxy benzaldehyde (THBA) via click chemistry and Schiff base reaction (COF-V@GSH-THBA-Ti⁴⁺) was constructed and applied for selective enrichment of phosphopeptides in serum. Benefit from the high surface area, excellent hydrophilicity as well as regular mesoporous structure, COF-V@GSH-THBA-Ti⁴⁺ displayed high selectivity (molar ratio of 2000:1), low limit of detection (0.5 fmol), high load capacity (100.0 mg/g) and excellent size-exclusion effect (1:10000) for enrichment of phosphopeptides. For actual bio-sample analysis, 15 phosphopeptides assigned to 10 phosphoproteins with 16 phosphorylated sites and 33 phosphopeptides assigned to 25 phosphoproteins with 34 phosphorylated sites were detected from the serum of patients with chronic obstructive pulmonary disease (COPD), and normal controls. Biological processes and molecular functions analysis further disclosed the difference of serums with phosphoproteomics between COPD and normal controls.

中文翻译：

---

点击化学和希夫碱反应的结合：共价有机框架的后合成作为固定金属离子亲和层析平台，用于有效捕获慢性阻塞性肺疾病血清中的整体磷酸肽

功能化材料的合理设计和构建对于富集全局磷酸肽具有重要意义。在这项工作中，通过点击化学和希夫碱反应引入谷胱甘肽（GSH）和2,3,4-三羟基苯甲醛（THBA）， Ti ^{4+功能化了亲水性共价有机框架（COF-V@GSH-THBA-Ti 4+}）构建并应用于血清中磷酸肽的选择性富集。得益于高比表面积、优异的亲水性以及规则的介孔结构，COF-V@GSH-THBA-Ti ⁴⁺表现出高选择性（摩尔比为 2000:1）、低检测限（0.5 fmol）、高负载量富集磷酸肽的容量（100.0 mg/g）和出色的尺寸排阻效果（1:10000）。对于实际生物样品分析，从慢性阻塞性肺病（COPD）患者和正常对照的血清中检测到15种磷酸肽（分配给具有16个磷酸化位点的10种磷蛋白）和分配给25种磷蛋白（具有34个磷酸化位点）的33种磷酸肽。生物学过程和分子功能分析进一步揭示了COPD与正常对照之间血清磷酸化蛋白质组学的差异。