Glutamine Deamidation: Differentiation of Glutamic Acid and γ-Glutamic Acid in Peptides by Electron Capture Dissociation

Due to its much slower deamidation rate compared to that of asparagine (Asn), studies on glutamine (Gln) deamidation have been scarce, especially on the differentiation of its isomeric deamidation products: α- and γ-glutamic acid (Glu). It has been shown previously that electron capture dissociation (ECD) can be used to generate diagnostic ions for the deamidation products of Asn: aspartic acid (Asp) and isoaspartic acid (isoAsp). The current study explores the possibility of an extension of this ECD based method to the differentiation of the α- and γ-Glu residues, using three human Crystallin peptides (αA (1-11), βB2 (4-14), and γS (52-71)) and their potentially deamidated forms as model peptides. It was found that the z•-72 ions can be used to both identify the existence and locate the position of the γ-Glu residues. When the peptide contains a charge carrier near its N-terminus, the c+57 and c+59 ions may also be generated at the γ-Glu residue. It was unclear whether formation of these N-terminal diagnostic ions is specific to the Pro-γ-Glu sequence. Unlike the Asp containing peptides, the Glu containing peptides generally do not produce diagnostic side chain loss ions, due to the instability of the resulting radical. The presence of Glu residue(s) may be inferred from the observation of a series of zn•-59 ions, although it was neither site specific nor without interference from the γ-Glu residues. Finally, several interference peaks exist in the ECD spectra, which highlights the importance of the use of high performance mass spectrometers for confident identification of γ-Glu residues

Glutamine Deamidation: Differentiation of Glutamic Acid and γ-Glutamic Acid in Peptides by Electron Capture Dissociation

Due to its much slower deamidation rate compared to that of asparagine (Asn), studies on glutamine (Gln) deamidation have been scarce, especially on the differentiation of its isomeric deamidation products: α- and γ-glutamic acid (Glu). It has been shown previously that electron capture dissociation (ECD) can be used to generate diagnostic ions for the deamidation products of Asn: aspartic acid (Asp) and isoaspartic acid (isoAsp). The current study explores the possibility of an extension of this ECD based method to the differentiation of the α- and γ-Glu residues, using three human Crystallin peptides (αA (1-11), βB2 (4-14), and γS (52-71)) and their potentially deamidated forms as model peptides. It was found that the z•-72 ions can be used to both identify the existence and locate the position of the γ-Glu residues. When the peptide contains a charge carrier near its N-terminus, the c+57 and c+59 ions may also be generated at the γ-Glu residue. It was unclear whether formation of these N-terminal diagnostic ions is specific to the Pro-γ-Glu sequence. Unlike the Asp containing peptides, the Glu containing peptides generally do not produce diagnostic side chain loss ions, due to the instability of the resulting radical. The presence of Glu residue(s) may be inferred from the observation of a series of zn•-59 ions, although it was neither site specific nor without interference from the γ-Glu residues. Finally, several interference peaks exist in the ECD spectra, which highlights the importance of the use of high performance mass spectrometers for confident identification of γ-Glu residues

Differentiating N-Terminal Aspartic and Isoaspartic Acid Residues in Peptides

Formation of isoaspartic acid (isoAsp) is a common modification of aspartic acid (Asp) or asparagine (Asn) residue in proteins. Differentiation of isoAsp and Asp residues is a challenging task owing to their similar properties and identical molecular mass. It was recently shown that they can be differentiated using ion–electron or ion–ion interaction fragmentation methods (ExD) because these methods provide diagnostic fragments c + 57 and z• – 57 specific to the isoAsp residue. To date, however, the presence of such fragments has not been explored on peptides with an N-terminal isoAsp residue. To address this question, several N-terminal isoAsp-containing peptides were analyzed using ExD methods alone or combined with chromatography. A diagnostic fragment [M + 2H – 74]+• was observed for the doubly charged precursor ions with N-terminal isoAsp residues. For some peptides, identification of the N-terminal isoAsp residue was challenging because of the low diagnostic ion peak intensity and the presence of interfering peaks. Supplemental activation was used to improve diagnostic ion detection. Further, N-terminal acetylation was offered as a means to overcome the interference problem by shifting the diagnostic fragment peak to [M + 2H – 116]+•

Additional file 1 of Optimizing the treatment mode for de novo metastatic nasopharyngeal carcinoma with bone-only metastasis

Additional file 1: Figure S1 Kaplan-Meier curves for OS of 131 patients with de novo metastatic NPC based on whether patients received RT to metastatic bone lesions or not that was divided by the cut-off values of 1 (a and b) and 3 bone metastases (c and d)

Prediction and Structure–Activity Relationship Analysis on Ready Biodegradability of Chemical Using Machine Learning Method

Persistent contaminants from different industries have already caused significant risks to the environment and public health. In this study, a data set containing 1306 not readily biodegradable (NRB) and 622 readily biodegradable (RB) chemicals was collected and characterized by CORINA descriptors, MACCS fingerprints, and ECFP_4 fingerprints. We utilized decision tree (DT), support vector machine (SVM), random forest (RF), and deep neural network (DNN) to construct 34 classification models that could predict the biodegradability of compounds. The best model (model 5F) built using a Transformer-CNN algorithm had a balanced accuracy of 86.29% and a Matthews correlation coefficient of 0.71 on the test set. By analyzing the top 10 CORINA descriptors used for modeling, the properties containing solubility, π/σ atom charges, rotatable bonds number, lone pair/π/σ atom electronegativities, molecular weight, and number of nitrogen atom based hydrogen bonding acceptors were determined to be critical for biodegradability. The substructure investigations confirmed earlier studies that the presence of aromatic rings and nitrogen or halogen substitutions in a molecule will hinder the biodegradation of the compound, while the ester groups and carboxyl groups promote biodegradability. We also identified the representative fragments affecting biodegradability by analyzing the frequency differences of substructural fragments between the NRB and RB compounds. The results of the study can provide excellent guidance for the discovery and design of compounds with good chemical biodegradability

Additional file 2 of RNF38 suppress growth and metastasis via ubiquitination of ACTN4 in nasopharyngeal carcinoma

Additional file 2: Figure S2. Gene Ontology (GO) analysis (A) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis (B) of significantly enriched proteins in RNF38-overexpressing CNE-2 cells

Energy-Dependent Electron Activated Dissociation of Metal-Adducted Permethylated Oligosaccharides

The effects of varying the electron energy and cationizing agents on electron activated dissociation (ExD) of metal-adducted oligosaccharides were explored, using permethylated maltoheptaose as the model system. Across the examined range of electron energy, the metal-adducted oligosaccharide exhibited several fragmentation processes, including electron capture dissociation (ECD) at low energies, hot-ECD at intermediate energies, and electronic excitation dissociation (EED) at high energies. The dissociation threshold depended on the metal charge carrier(s), whereas the types and sequence spans of product ions were influenced by the metal-oligosaccharide binding pattern. Theoretical modeling contributed insight into the metal-dependent behavior of carbohydrates during low-energy ECD. When ExD was applied to a permethylated high mannose N-linked glycan, EED provided more structural information than either collision-induced dissociation (CID) or low-energy ECD, thus demonstrating its potential for oligosaccharide linkage analysis

Additional file 2 of Optimizing the treatment mode for de novo metastatic nasopharyngeal carcinoma with bone-only metastasis

Additional file 2: Supplementary Table 1 Univariable and Multivariate analysis for OS in de novo mNPC patients classified by number of metastatic

Additional file 3 of RNF38 suppress growth and metastasis via ubiquitination of ACTN4 in nasopharyngeal carcinoma

Additional file 3: Supplementary Table S1. Comparison of RNF38 expression between nasopharyngeal carcinoma and normal nasopharyngeal epithelia tissues

Additional file 1 of RNF38 suppress growth and metastasis via ubiquitination of ACTN4 in nasopharyngeal carcinoma

Additional file 1: Figure S1. Gene Ontology (GO) analysis (A) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis (B) of significantly enriched proteins in RNF38-overexpressing SUNE-1 cells