Bioinspired Saccharide-Saccharide Interaction and Smart Polymer for Specific Enrichment of Sialylated Glycopeptides
Bioinspired Saccharide-Saccharide Interaction and Smart Polymer for Specific Enrichment of Sialylated Glycopeptides
复制标题
用于特异性富集唾液酸化糖肽的仿生糖-糖相互作用和智能聚合物
DOI：
10.1021/acsami.6b03104
复制
发表时间：
2016-06-01
影响因子：
9.5
通讯作者：
Liang, Xinmiao
中科院分区：
文献类型：
--
作者：
Li, Xiuling;Xiong, Yuting;Liang, Xinmiao
蛋白质的异常唾液酸化与许多主要疾病高度相关，例如癌症和神经退行性疾病。然而，由于难以从高度复杂的生物样品中富集痕量唾液酸化糖肽（SG），因此这项研究具有挑战性。解决这一问题的关键很大程度上依赖于新型 SG 受体的设计，以特定且可调节的方式捕获唾液酸 (SA) 部分。受生命系统中糖-糖相互作用的启发，我们将基于糖的 SG 受体引入本研究中。阿洛糖（一种单糖）对 SA 表现出特异性且 pH 敏感的结合。将阿洛糖单元整合到聚丙烯酰胺链中生成糖响应智能共聚物（SRSC）。这样的设计显着提高了SA结合的选择性；同时，这种结合在很大程度上可以由溶液极性和pH值智能触发。因此，即使在牛血清白蛋白消化物500倍的干扰下，SRSC仍表现出对SGs的高性能富集能力，明显高于传统材料。在 HeLa 细胞裂解物的真实生物样品中，使用 SRSC 鉴定出了 180 个唾液酸化糖基化位点 (SGS)。这显然优于通过 SA 结合凝集素（包括 WGA（18 个 SGS）和 SNA（22 个 SGS））获得的结果。此外，乳糖对多种二糖表现出良好的化学选择性，这表明乳糖基材料在聚糖辨别方面具有良好的潜力。随后，基于乳糖的 SRSC 有助于通过 CH3CN/H2O 梯度逐步分离具有相同肽序列但不同聚糖的 O-连接或 N-连接 SG。这项研究为下一代糖肽富集材料开辟了新途径。
Abnormal sialylation of proteins is highly associated with many major diseases, such as cancers and neurodegenerative diseases. However, this study is challenging owing to the difficulty in enriching trace sialylated glycopeptides (SGs) from highly complex biosamples. The key to solving this problem relies strongly on the design of novel SG receptors to capture the sialic acid (SA) moieties in a specific and tunable manner. Inspired by the saccharide-saccharide interactions in life systems, here we introduce saccharide-based SG receptors into this study. Allose (a monosaccharide) displays specific and pH-sensitive binding toward SAs. Integrating allose units into a polyacrylamide chain generates a saccharide-responsive smart copolymer (SRSC). Such design significantly improves the selectivity of SA binding; meanwhile, this binding can be intelligently triggered in a large extent by solution polarity and pH. As a result, SRSC exhibits high-performance enrichment capacity toward SGs, even under 500-fold interference of bovine serum albumins digests, which is notably higher than conventional materials. In real biosamples of HeLa cell lysates, 180 sialylated glycosylation sites (SGSs) have been identified using SRSC. This is apparently superior to those obtained by SA-binding lectins including WGA (18 SGSs) and SNA (22 SGSs). Furthermore, lactose displays good chemoselectivity toward diverse disaccharides, which indicated the good potential of lactose-based material in glyean discrimination. Subsequently, the lactose-based SRSC facilitates the stepwise isolation of O-linked or N-linked SGs with the same peptide sequence but varied glycans by CH3CN/H2O gradients. This study opens a new avenue for next generation of glycopeptide enrichment materials.