title: Synthesis of zwitterionic polymer brushes hybrid silica nanoparticles via controlled polymerization for highly efficient enrichment of glycopeptides.
abstract: Zwitterionic hydrophilic interaction chromatography (ZIC-HILIC) materials have been increasingly attractive in glycopeptide enrichment. However, the traditional ZIC-HILIC materials are modified with monolayer zwitterionic molecules on the surface, therefore, the hydrophilicity, detection sensitivity and loading capacity are limited. In this work, we synthesized novel silica nanoparticles with uniform poly(2-(methacryloyloxy)ethyl)dimethyl-(3-sul-fopropyl)ammonium hydroxide (PMSA) brushes grafted onto the surface via reversible addition-fragmentation chain transfer (RAFT) polymerization (denoted as SiO2-RAFT@PMSA). The resulting SiO2-RAFT@PMSA nanoparticles demonstrated low detection limit (10 fmol) and high recovery yield (over 88%) for glycopeptide enrichment from tryptic digest of human IgG. The SiO2-RAFT@PMSA nanoparticles were further applied for the analysis of mouse liver glycoproteome, a total number of 303 unique N-glycosylation sites corresponding to 185 glycoproteins was reliably profiled in three replicate nano-LC-MS/MS runs. Significantly, more glycopeptides were identified than those of nanoparticles, monolayer MSA molecules modified SiO2@single-MSA and nonuniform multi-layer PMSA brushes coated SiO2@PMSA, as well as commercial ZIC@HILIC beads and Click Maltose beads. The excellent performance of SiO2-RAFT@PMSA nanoparticles results from the non-fouling property, a large quantity of functional molecules and suitable link arms provided by uniform PMSA brushes, as well as efficient interaction between glycopeptides and uniform PMSA brushes. It is concluded that the synthesized SiO2-RAFT@PMSA nanoparticles exhibit great potential in glycoproteome analysis. Moreover, this strategy to modify nanopaticles with uniform polymer brushes via RAFT polymerization can also be explored to design other types of materials for bioseparation application.
authors.affiliation: CAS Key Laboratory of Separation Science for Analytical Chemistry, National Chromatographic R & A Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences (CAS), Dalian 116023, China; University of Chinese Academy of Sciences, Beijing 100049, China; State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Huang
authors.affiliation: CAS Key Laboratory of Separation Science for Analytical Chemistry, National Chromatographic R & A Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences (CAS), Dalian 116023, China; Shanghai Key Laboratory of Functional Materials Chemistry, East China University of Science and Technology, Shanghai 20023, China.
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Xiong
authors.affiliation: CAS Key Laboratory of Separation Science for Analytical Chemistry, National Chromatographic R & A Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences (CAS), Dalian 116023, China.
authors.forename: Hongqiang
authors.initials: H
authors.lastname: Qin
authors.affiliation: CAS Key Laboratory of Separation Science for Analytical Chemistry, National Chromatographic R & A Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences (CAS), Dalian 116023, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
authors.affiliation: CAS Key Laboratory of Separation Science for Analytical Chemistry, National Chromatographic R & A Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences (CAS), Dalian 116023, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Sun
authors.affiliation: CAS Key Laboratory of Separation Science for Analytical Chemistry, National Chromatographic R & A Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences (CAS), Dalian 116023, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Peng
authors.affiliation: CAS Key Laboratory of Separation Science for Analytical Chemistry, National Chromatographic R & A Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences (CAS), Dalian 116023, China. Electronic address: junjieou@dicp.ac.cn.
authors.forename: Junjie
authors.initials: J
authors.lastname: ou
authors.affiliation: CAS Key Laboratory of Separation Science for Analytical Chemistry, National Chromatographic R & A Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences (CAS), Dalian 116023, China. Electronic address: hanfazou@dicp.ac.cn.
authors.forename: Hanfa
authors.initials: H
authors.lastname: Zou
mesh_terms: D000818:Animals; D006020:Glycopeptides / Q000032:analysis / Q000302:isolation & purification*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000737:chemistry; D008099:Liver / Q000737:chemistry; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D058105:Polymerization; D011108:Polymers / Q000138:chemical synthesis* / Q000737:chemistry; D011109:Polymethacrylic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D012822:Silicon Dioxide / Q000737:chemistry*; D013499:Surface Properties
chemical_list: D006020:Glycopeptides; D007074:Immunoglobulin G; D011108:Polymers; D011109:Polymethacrylic Acids; D000644:Quaternary Ammonium Compounds; D012822:Silicon Dioxide
keywords: Controlled polymerization; Glycopeptide enrichment; Glycoproteomics; Hydrophilic interaction chromatography; Silica nanoparticles