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Chemical modification of covalent organic frameworks(COFs) is indispensable for integrating functionalities of greatercomplexity and accessing advanced COF materials suitable for morepotential applications. Reported here is a novel strategy for fabricatingcontrollable core?shell structured Zr4+-immobilized magnetic COFs(MCNC@COF@Zr4+) composed of a high-magnetic-response mag-netic colloid nanocrystal cluster (MCNC) core, Zr4+ion-functionalizedtwo-dimensionalCOFsastheshellbysequentialpostsyntheticfunctionalization and, for thefirst time, the application of theMCNC@COF@Zr4+composites for efficient and selective enrichmentof phosphopeptides. The as-prepared MCNC@COF@Zr4+compositespossess regular porosity with large surface areas, high Zr4+loadingamount, strong magnetic responsiveness, and good thermal/chemicalstability, which can serve as an ideal adsorbent for selective enrichmentof phosphopeptides and simultaneous size exclusion of biomacromolecules, such as proteins. The high detection sensitivity (10fmol) together with the excellent recovery of phosphopeptides is also obtained. These outstanding features suggest that theMCNC@COF@Zr4+composites are of great benefit for pretreatment prior to mass spectrometry analysis of phosphopeptides.In addition, the performance of the developed approach in selective enrichment of phosphopeptides from the tryptic digests ofdefatted milk and directly specific capture of endogenous phosphopeptides from human serum gives powerful proof for its highselectivity and effectiveness in identifying the low-abundance phosphopeptides from complicated biological samples. This studynot only provides a strategy for versatile functionalization of magnetic COFs but also opens a new avenue in their use inphosphoproteome analysis