Liu Shuai, Zhang Mo, Lai Zhizhen, Tian Hongtao, Qiu Yuming, Li Zhili
Department of Biophysics and Structural Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, 5 Dongdan San Tiao, Beijing 100005, China.
ACS Appl Mater Interfaces. 2022 Jul 27;14(29):32890-32900. doi: 10.1021/acsami.2c06922. Epub 2022 Jul 12.
To date, advanced chemical biology tools for chemoselective extraction of metabolites are limited. In this study, unique coral-like polymer particles were synthesized via high concentrations of 1-ethyl-3-(3-(dimethylamino)propyl) carbodiimide hydrochloride (EDC)/-hydroxysuccinimide (NHS), which are usually used as condensation agents. The polymers can wrap or adhere FeO nanoparticles (FeO-NPs) to form polymer magnetic microparticles (PMMPs). With abundant NHS-activated moieties on their surface, the coral-like PMMPs could be modified by cystamine for the chemoselective extraction of phosphate/carboxylate anion metabolites from complex biological samples. Finally, 97 metabolites including nucleotides, phosphates, phosphate sugars, carboxylate sugars, and organic acids were extracted and identified from serum, tissues, and cells. These metabolites are involved in four major metabolic pathways including glycolysis, the tricarboxylic acid cycle, the pentose phosphate pathway, and nucleotide metabolism. This study has provided a cost-effective and easy-to-implement preparation of PMMPs with a robust chemoselective extraction ability and versatile applications.
迄今为止,用于化学选择性提取代谢物的先进化学生物学工具十分有限。在本研究中,通过高浓度的1-乙基-3-(3-(二甲基氨基)丙基)碳二亚胺盐酸盐(EDC)/N-羟基琥珀酰亚胺(NHS)合成了独特的珊瑚状聚合物颗粒,这两种物质通常用作缩合剂。这些聚合物可以包裹或附着FeO纳米颗粒(FeO-NPs)以形成聚合物磁性微粒(PMMPs)。由于其表面有大量NHS活化基团,珊瑚状PMMPs可以用胱胺进行修饰,用于从复杂生物样品中化学选择性提取磷酸盐/羧酸盐阴离子代谢物。最后,从血清、组织和细胞中提取并鉴定出了97种代谢物,包括核苷酸、磷酸盐、磷酸糖、羧基糖和有机酸。这些代谢物参与糖酵解、三羧酸循环、磷酸戊糖途径和核苷酸代谢这四条主要代谢途径。本研究提供了一种经济高效且易于实施的PMMPs制备方法,其具有强大的化学选择性提取能力和广泛的应用。