Novel nanoporous covalent organic frameworks for the selective extraction of endogenous peptides

Endogenous peptides are important biomarkers, but their low abundance and abundant interference in biosamples impede their analysis. In this study, a novel nanoporous covalent organic framework (COF) was prepared and successfully applied for selective extraction of endogenous peptides from human serum. This novel COF exhibited strong retention and high adsorption capacity toward peptides, as well as efficient exclusion of large proteins, ascribed to its strong hydrophobicity, uniform pore size (∼2.5 nm) and large surface area (826.5 m² g^-1). These features facilitated the extraction of endogenous peptides from complex biosamples, resulting in 27 identified peptides from tryptic digests of bovine serum albumin (BSA) mixed with 1000 mass folds of BSA protein. Moreover, the adsorption rate of the peptides was 3.6-fold faster than that of proteins on this novel COF. After application the novel COF to 5 μL human serum, 416 unique peptides were unambiguously identified. These results demonstrated the excellent properties of the novel COF in extraction of endogenous peptides. We envisage that COFs with adjustable organic building units and unique physicochemical properties will qualify their potential applications in peptidomics research.