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The reasonable design of metal-organic framework (MOF)-derived nanomaterial has important meaning in increasing the enrichment efficiency in the study of protein phosphorylation. In this work, a polyoxometalate (POM) functionalized magnetic MOF nanomaterial (Fe 3 O 4 @MIL-125-POM) was designed and fabricated. The nanomaterial with multi-affinity sites (unsaturated metal sites and metal oxide clusters) was used for the enrichment of phosphopeptides. Fe 3 O 4 @MIL-125-POM had high-efficient enrichment performance towards phosphopeptides (selectivity, a mass ratio of bovine serum albumin/α-casein/β-casein at 5000:1:1; sensitivity, 0.1 fmol; satisfactory repeatability, ten times). Furthermore, Fe 3 O 4 @MIL-125-POM was employed to enrich phosphopeptides from non-fat milk digests, saliva, serum, and A549 cell lysate. The enrichment results illustrated the great potential of Fe 3 O 4 @MIL-125-POM for efficient identification of low-abundance phosphopeptides., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

In this study, titanium (IV)-immobilized magnetic nanoparticles (Ti 4+ -PTL-MNPs) were firstly synthesized via a one-step aqueous self-assembly of lysozyme nanofilms for efficient phosphopeptide enrichment. Under physiological conditions, lysozymes readily self-organized into phase-transitioned lysozyme (PTL) nanofilms on Fe 3 O 4 @SiO 2 and Fe 3 O 4 @C MNP surfaces with abundant functional groups, including -NH 2 , -COOH, -OH, and -SH, which can be used as multiple linkers to efficiently chelate Ti 4+ . The obtained Ti 4+ -PTL-MNPs possessed high sensitivity of 0.01 fmol μL -1 and remarkable selectivity even at a mass ratio of β-casein to BSA as low as 1:400 for phosphopeptide enrichment. Furthermore, the synthesized Ti 4+ -PTL-MNPs can also selectively identify low-abundance phosphopeptides from extremely complicated human serum samples and their rapid separation, good reproducibility, and excellent recovery were also proven. This one-step self-assembly of PTL nanofilms facilitated the facile and efficient surface functionalization of various nanoparticles for proteomes/peptidomes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

A new general approach called in situ digestion-assisted multi-template imprinting is proposed for preparation of phospho-specific molecularly imprinted nanoparticles. Through the novel templating strategy and controllable imprinting process, imprinted nanoparticles specific to the intact phosphoprotein and its phosphopeptides were synthesized. The prepared imprinted nanoparticles exhibited excellent specificity (cross reactivity < 10%), high affinity (10 -6  M), high efficiency (47.5%), and good generality (both intact phosphoprotein and phosphopeptides). We also realized the fine tuning of the recognition at peptide level of the imprinted nanoparticles by adjusting the imprinting time. Based on the selective enrichment of the imprinted nanoparticles, the MS identification of both the intact phosphoprotein (Tau) and phosphopeptides (angiotensin II and peptides of Tau) in real complex samples could be achieved. Therefore, we believe that the in situ digestion-assisted multi-template imprinting strategy holds promising future in both phosphorylation analysis and proteomics applications., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Cerium ions immobilized magnetic graphite nitride material have been prepared using L-Alanyl-L-Glutamine as the new chelator. The resulting Fe 3 O 4 /g-C 3 N 4 -L-Ala-L-Gln-Ce 4+ , as an immobilized metal ion affinity chromatography (IMAC) sorbent, was reusable. This is due to the strong coordination interaction between L-Alanyl-L-Glutamine and cerium ions. After a series of characterizations, the magnetic nanocomposite showed high surface area, good hydrophilicity, positive electricity, and magnetic response. Fe 3 O 4 /g-C 3 N 4 -L-Ala-L-Gln-Ce 4+ had high sensitivity (0.1 fmol), selectivity (α-/β-casein/bovine serum albumin, 1:1:5000), and good recyclability (10 cycles). A total of 647 unique phosphopeptides mapped to 491 phosphoproteins were identified from A549 cell lysate by nano LC-MS analysis., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Animal-derived drugs are an indispensable part of folk medicine worldwide. However, their chemical constituents are poorly approached, which leads to the low level of the quality standard system of animal-derived drugs and further causes a chaotic market. Natural peptides are ubiquitous throughout the organism, especially in animal-derived drugs. Thus, in this study, we used multi-source leeches, including Hirudo nipponica (HN), Whitmania pigra (WP), Whitmania acranulata (WA), and Poecilobdella manillensis (PM), as a model. A strategy integrating proteogenomics and novel pseudotargeted peptidomics was developed to characterize the natural peptide phenotype and screen for signature peptides of four leech species. First, natural peptides were sequenced against an in-house annotated protein database of closely related species constructed from RNA-seq data from the Sequence Read Archive (SRA) website, which is an open-sourced public archive resource. Second, a novel pseudotargeted peptidomics integrating peptide ion pair extraction and retention time transfer was established to achieve high coverage and quantitative accuracy of the natural peptides and to screen for signature peptides for species authentication. In all, 2323 natural peptides were identified from four leech species whose databases were poorly annotated. The strategy was shown to significantly improve peptide identification. In addition, 36 of 167 differential peptides screened by pseudotargeted proteomics were identified, and about one-third of them came from the leucine-rich repeat domain (LRR) proteins, which are widely distributed in organisms. Furthermore, six signature peptides were screened with good specificity and stability, and four of them were validated by synthetic standards. Finally, a dynamic multiple reaction monitoring (dMRM) method based on these signature peptides was established and revealed that one-half of the commercial samples and all of the Tongxinluo capsules were derived from WP. All in all, the strategy developed in this study was effective for natural peptide characterization and signature peptide screening, which could also be applied to other animal-derived drugs, especially for modelless species that are less studied in protein database annotation., (© 2023. Springer-Verlag GmbH Germany, part of Springer Nature.)

For the first time a hybrid molecularly imprinted polymer (MIP) doped with 3-(trimethoxysilyl) propyl methacrylate (γ-MPS)-modified mesoporous molecular sieve SBA-15 for target peptide recognition has been developed. Zinc acrylate and methacrylic acid were used as binary functional monomers, and ethylene dimethacrylate was used as cross-linking agent to prepare an imprinted monolith against Val-Tyr-Ala-Leu-Lys(glutarylation) (VYALK glu ). The morphology of the polymers was characterized by scanning electron microscopy, FT-IR spectroscopy, energy dispersive spectroscopy, and 1 H NMR. The SBA-15-MPS MIP showed high recovery of 87.1% and the IF of 12.9 for the enrichment of the template peptide. When the template peptide concentration ranged from 5 to 90 μg mL -1 , the correlation coefficients (R 2 ) for the calibration function obtained was better 0.999. The limit of detection (LOD, 0.30 μg mL -1 ) and limit of quantification (LOQ, 1.0 μg mL -1 ) were achieved for signal-to-noise ratios of 3:1 and 10:1, respectively. When other kinds of synthetic peptides were used as analogs, the selectivity of the SBA-15-MPS MIP was much better than the SBA-15-MPS NIP (without template peptides) with relative selectivity coefficients of 52.8-265. In contrast, little quinolones and biogenic amines are adsorbed with the SBA-15-MPS MIP. The SBA-15-MPS MIP could enrich VYALK glu from spiked histone digestion with the average recovery of 87.8% and the relative standard deviation (RSD) of 0.99%. As a conclusion, doping of SBA-15 is an effective approach to the improvement of performance of molecularly imprinted monolith., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Cancer is a collection of diseases caused by specific changes at the genomic level that support cell proliferation indefinitely. Traditionally, ion channels are known to control a variety of cellular processes including electrical signal generation and transmission, secretion, and contraction by controlling ionic gradients. However, recent studies had brought to light important facts on ion channels in cancer biology.In this review we discuss the mechanism linking potassium or chloride ion channel activity to biochemical pathways controlling proliferation in cancer cells and the potential advantages of targeting ion channels as an anticancer therapeutic option., (© 2021. Springer Nature Switzerland AG.)

Head and neck cancers are a highly complex and heterogeneous group of malignancies that involve very diverse anatomical structures and distinct aetiological factors, treatments and clinical outcomes. Among them, head and neck squamous cell carcinomas (HNSCC) are predominant and the sixth most common cancer worldwide with still low survival rates. Omic technologies have unravelled the intricacies of tumour biology, harbouring a large diversity of genetic and molecular changes to drive the carcinogenesis process. Nonetheless, this remarkable heterogeneity of molecular alterations opens up an immense opportunity to discover novel biomarkers and develop molecular-targeted therapies. Increasing evidence demonstrates that dysregulation of ion channel expression and/or function is frequently and commonly observed in a variety of cancers from different origin. As a consequence, the concept of ion channels as potential membrane therapeutic targets and/or biomarkers for cancer diagnosis and prognosis has attracted growing attention. This chapter intends to comprehensively and critically review the current state-of-art ion channel dysregulation specifically focusing on head and neck cancers and to formulate the major challenges and research needs to translate this knowledge into clinical application. Based on current reported data, various voltage-gated potassium (K v ) channels (i.e. K v 3.4, K v 10.1 and K v 11.1) have been found frequently aberrantly expressed in HNSCC as well as precancerous lesions and are highlighted as clinically and biologically relevant features in both early stages of tumourigenesis and late stages of disease progression. More importantly, they also emerge as promising candidates as cancer risk markers, tumour markers and potential anti-proliferative and anti-metastatic targets for therapeutic interventions; however, the oncogenic properties seem to be independent of their ion-conducting function., (© 2020. Springer Nature Switzerland AG.)