Designed synthesis of a \u201cOne for Two\u201d hydrophilic magnetic amino-functionalized metal-organic framework for highly efficient enrichment of glycopeptides and phosphopeptides

Yiqin Xie,Chunhui Deng

doi:10.1038/s41598-017-01341-y

Abstract

Highly efficient enrichment of glycopeptides or phosphopeptides from complex biological samples is indispensable for high-throughput mass spectrometry analysis. In this study, for the first time, a “one for two” hydrophilic magnetic amino-functionalized metal-organic framework (MOF) was designed and synthesized for selective enrichment of both glycopeptides and phosphopeptides. A well-known solvo-thermal reaction was adopted to prepare a magnetic core Fe3O4, followed by self- polymerization of dopamine, creating a polydopamine (PDA) onto Fe3O4. Thanks to the hydroxyl and amino group of PDA, Zr3+ was easily adhered to the surface, inducing the following one-pot MOF reaction with amino ligand. After characterization of the as-prepared MOFs (denoted as Fe3O4@PDA@UiO-66-NH2), its ultrahigh surface area, excellent hydrophilicity and strong magnetic responsiveness were highly confirmed. Based on hydrophilic interaction, it was applied to glycopeptide enrichment, while based on strong binding between Zr and phosphopeptides, it was applied to phosphopeptide enrichment, both exhibiting excellent performance in standard proteins and human serum with high sensitivity and selectivity. These results showed the as-prepared MOFs had great potential in proteomics research.

Highlights

Protein glycosylation and phosphorylation, two of the most important post-translational modifications (PTMs), play a critical role in many biological processes, such as signal transduction[1], cell-cell interaction[2], cell adhesion[3], and so on
To improve the enrichment performance, reduce the trouble in synthesis and cut the time in separation, a facile route was first proposed for preparation of a “One for Two” hydrophilic magnetic amino-functionalized metal-organic framework by modifying UiO-66-NH2 (Zr-MOF) onto the polydopamine (PDA)-coated magnetic microspheres (Fe3O4@PDA@UiO-66-NH2)
energy dispersive X-ray (EDX) analysis of Fe3O4@PDA@UiO-66-NH2 further confirmed the existence of Zr. (Supporting Information Figure S2) Transmission electron microscopy (TEM) image (Fig. 1c) of Fe3O4@PDA@UiO-66-NH2 shows that MOF shell is grafted onto the Fe3O4@PDA nanoparticles and PDA@MOF shell-shell is around 70 nm with the Fe3O4 core unchanged

Summary

Introduction

Two of the most important post-translational modifications (PTMs), play a critical role in many biological processes, such as signal transduction[1], cell-cell interaction[2], cell adhesion[3], and so on. HILIC materials, including metal-organic frameworks[22], monoliths[23], and nanoparticles[24], have been regarded as the most potential materials for glycopeptide enrichment with excellent performance, and could be applied to phosphopeptide enrichment based on IMAC techniques, which aroused great interest and popularity due to handy operation, simple enrichment process, low bias to different types of peptides, and mild conditions for MS analysis[25]. Metal–organic frameworks have been applied to proteomics, such as, endogenous peptide enrichment[29], glycopeptide enrichment[30, 31], enzyme immobilization[32], etc For this reason, a new spot hit our head to create a promising material, combining the hydrophilic interaction, IMAC techniques and MOF, further applied to glycoproteome and phosphoproteome analysis. The as-prepared MOFs exhibited strong magnetic responsiveness and excellent hydrophilicity and strong binding between Zr and phosphopeptides, so a promising future for excellent performance in glycopeptide and phosphopeptide enrichment could be anticipated

Methods

Results

Conclusion