Phosphopeptide enrichment with high selectivity and detection sensitivity is essential for phosphoproteomic studies and remains a long-standing challenge. In this study, new immobilized metal affinity chromatography nanocomposite adsorbents with a phosphonate-functionalized ionic liquid (PFIL) as a surface modifier are successfully prepared via a reaction sequence of amination, quaternization, phosphonate hydrolyzation, and metal immobilization. Taking advantages of integrated features of a flexible and strong tripodal phosphonate chelator, a hydrophilic ionic liquid linker, a large surface area, and the size-exclusion effect, the resulting nanocomposite G@mSiO 2 -PFIL-Ti 4+ exhibits excellent detection sensitivity to enrich phosphorylated peptides from a tryptic β-casein digest (0.15 fmol), and superior enrichment selectivity to capture phosphorylated peptides from a digest mixture of β-casein and bovine serum albumin (a molar ratio of 1:10,000). Strong immobilization of tripodal chelation to metal ions endows the nanocomposite adsorbent with high tolerance to experimental conditions, and thus excellent reusability of the adsorbent has been achieved without remarkable loss of enrichment efficiency for 10 cycles. Due to the excellent size-exclusion effect, high enrichment specificity of G@mSiO 2 -PFIL-Ti 4+ to phosphopeptides has been observed and 23 endogenous phosphopeptides have been captured from human saliva. In addition, 924 phosphopeptides (enrichment specificity, 56.1%) have been identified from the tryptic digest of mouse brain lysate. Particularly, six of 975 phosphorylation sites were Alzheimer's disease-related hyperphosphorylation sites within tau protein. These results demonstrate that G@mSiO 2 -PFIL-Ti 4+ nanocomposite affinity materials show great application potential for a proteomic study of complicated biological samples.
A new methodology for the synthesis of fascaplysin derivatives has been established. A library of diversified fascaplysins can be efficiently and quickly prepared by regioselective Suzuki‐Miyaura coupling and subsequent quaternization for the first time. The minimum inhibitory concentration assessment showed that the unique 5‐ring coplanar aromatic system plays a key role in the resulting bioactivity, and functional groups at different substitution position exert differentiable impact on the bactericidal activity. some synthesized fascaplysin derivatives exhibited higher antibacterial activities than the pristine fascaplysin and the positive controls, especially against Gram‐negative bacteria Escherichia coli (ATCC 25922). These novel fascaplysin derivatives may have promising application potentials as bactericidal drugs.
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