title: Titanium (IV) ion-modified covalent organic frameworks for specific enrichment of phosphopeptides.
abstract: To date, plenty of new alternative materials for phosphopeptides enrichment prior to mass spectrometry (MS) analysis appear, especially immobilized metal ion affinity chromatography (IMAC) materials. The variable combinations with different metal ions, chelating ligands and solid supports offer full of optionality for IMAC. However, further improvement was predicted by the tedious and complex synthetic process. In this work, a novel covalent organic framework (COF)-based IMAC material (denoted TpPa-2-Ti4+) was prepared simply by direct immobilizing Ti (IV) into TpPa-2 COFs without any extra chelating ligands. The structure and composition of as-prepared composites were confirmed by PXRD, FT-IR and XPS, and a new flower-shaped Ti4+-IMAC with regular micro-nano hierarchical structure was observed in the SEM and TEM images. The obtained titanium (IV) ion-modified covalent organic frameworks demonstrated low limit of detection (4 fmol) and largely-satisfactory selectivity (β-casein: BSA=1:100) for phosphopeptide capturing from β-casein. Similarly, 18 and 17 phosphopeptides could be easily detected in the tryptic digest of α-casein or the digest mixture of α-casein and BSA (1:50). They were also successfully applied for enrichment of phosphopeptides from non-fat milk and HeLa cells with high sensitivity and satisfactory selectivity. All above results showed that the new titanium (IV) ion-modified covalent organic framework is expected to be a potential IMAC for phosphopeptide enrichment in large-scale phosphoproteomics studies.
authors.affiliation: Key Laboratory of Synthetic and Natural Function Molecule Chemistry of Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an 710069, China; State Key Laboratory of Proteomics, National Center for Protein Science Beijing, Beijing Institute of Radiation Medicine, Beijing 102206, China.
authors.forename: Heping
authors.initials: H
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Proteomics, National Center for Protein Science Beijing, Beijing Institute of Radiation Medicine, Beijing 102206, China.
authors.forename: Fenglong
authors.initials: F
authors.lastname: Jiao
authors.affiliation: State Key Laboratory of Proteomics, National Center for Protein Science Beijing, Beijing Institute of Radiation Medicine, Beijing 102206, China.
authors.forename: Fangyuan
authors.initials: F
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Proteomics, National Center for Protein Science Beijing, Beijing Institute of Radiation Medicine, Beijing 102206, China.
authors.forename: Yayao
authors.initials: Y
authors.lastname: Lv
authors.affiliation: State Key Laboratory of Proteomics, National Center for Protein Science Beijing, Beijing Institute of Radiation Medicine, Beijing 102206, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Proteomics, National Center for Protein Science Beijing, Beijing Institute of Radiation Medicine, Beijing 102206, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Synthetic and Natural Function Molecule Chemistry of Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an 710069, China. Electronic address: yhshen@nwu.edu.cn.
authors.forename: Yehua
authors.initials: Y
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Proteomics, National Center for Protein Science Beijing, Beijing Institute of Radiation Medicine, Beijing 102206, China. Electronic address: 13683167093@163.com.
authors.forename: Yangjun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Proteomics, National Center for Protein Science Beijing, Beijing Institute of Radiation Medicine, Beijing 102206, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Qian
mesh_terms: D000818:Animals; D002417:Cattle; D006367:HeLa Cells; D006801:Humans; D000073396:Metal-Organic Frameworks / Q000737:chemistry*; D010748:Phosphopeptides / Q000737:chemistry* / Q000378:metabolism; D040901:Proteomics / Q000379:methods* / Q000592:standards; D012015:Reference Standards; D014025:Titanium / Q000737:chemistry*
chemical_list: D000073396:Metal-Organic Frameworks; D010748:Phosphopeptides; D014025:Titanium
keywords: Covalent organic frameworks; Immobilized metal ion affinity chromatography; Phosphopeptide enrichment