Zhao Yanqing, Li Hongbin, Zheng Haijiao, Jia Qiong
College of Chemistry, Jilin University, Changchun 130012, China.
Anal Chem. 2025 Jan 21;97(2):1135-1142. doi: 10.1021/acs.analchem.4c04025. Epub 2025 Jan 7.
Smart-responsive materials have attracted much attention in the enrichment of post-translational modifications of proteins. In this work, for the first time, we developed a smart enrichment strategy (MNPs-l-DOPA/PEI-SP) based on the change in hydrophilic properties of spiropyran under the regulation of light and pH to realize the controllable enrichment and release of intact glycopeptides. The enrichment mechanism and possible binding mechanism were verified by theoretical calculations. The smart enrichment platform based on MNPs-l-DOPA/PEI-SP was used to screen glycoprotein biomarkers for hepatocellular carcinoma (HCC) to evaluate its cancer diagnostic and monitoring performance. A total of 3,864 intact -glycopeptides containing 166 -glycoproteins were successfully identified in serum samples of early-stage HCC patients, while 3,266 intact -glycopeptides containing 193 glycoproteins were identified in normal control (NC) serum samples. This work not only provides new ideas for the efficient enrichment of intact glycopeptides with smart-responsive material, but also broadens the research possibilities for biomarker discovery in HCC serum liquid biopsies.
智能响应材料在蛋白质翻译后修饰的富集方面备受关注。在这项工作中，我们首次基于螺吡喃在光和pH调节下亲水性的变化，开发了一种智能富集策略（MNPs-l-DOPA/PEI-SP），以实现完整糖肽的可控富集和释放。通过理论计算验证了富集机制和可能的结合机制。基于MNPs-l-DOPA/PEI-SP的智能富集平台用于筛选肝细胞癌（HCC）的糖蛋白生物标志物，以评估其癌症诊断和监测性能。在早期HCC患者的血清样本中成功鉴定出总共3864种包含166种糖蛋白的完整糖肽，而在正常对照（NC）血清样本中鉴定出3266种包含193种糖蛋白的完整糖肽。这项工作不仅为利用智能响应材料高效富集完整糖肽提供了新思路，也拓宽了HCC血清液体活检中生物标志物发现的研究可能性。
