scholarly journals Empirical Evaluation of the Use of Computational HLA Binding as an Early Filter to the Mass Spectrometry-Based Epitope Discovery Workflow

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2307
Author(s):  
Rachid Bouzid ◽  
Monique T. A. de Beijer ◽  
Robbie J. Luijten ◽  
Karel Bezstarosti ◽  
Amy L. Kessler ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Human Cancer ◽  
Empirical Evaluation ◽  
Peptide Identification ◽  
Binding Prediction ◽  
False Discovery Rates ◽  
Human Cancer Cell Lines ◽  
Liquid Chromatography Tandem Mass ◽  
Epitope Discovery ◽  
Hla Binding

Immunopeptidomics is used to identify novel epitopes for (therapeutic) vaccination strategies in cancer and infectious disease. Various false discovery rates (FDRs) are applied in the field when converting liquid chromatography-tandem mass spectrometry (LC-MS/MS) spectra to peptides. Subsequently, large efforts have recently been made to rescue peptides of lower confidence. However, it remains unclear what the overall relation is between the FDR threshold and the percentage of obtained HLA-binders. We here directly evaluated the effect of varying FDR thresholds on the resulting immunopeptidomes of HLA-eluates from human cancer cell lines and primary hepatocyte isolates using HLA-binding algorithms. Additional peptides obtained using less stringent FDR-thresholds, although generally derived from poorer spectra, still contained a high amount of HLA-binders and confirmed recently developed tools that tap into this pool of otherwise ignored peptides. Most of these peptides were identified with improved confidence when cell input was increased, supporting the validity and potential of these identifications. Altogether, our data suggest that increasing the FDR threshold for peptide identification in conjunction with data filtering by HLA-binding prediction, is a valid and highly potent method to more efficient exhaustion of immunopeptidome datasets for epitope discovery and reveals the extent of peptides to be rescued by recently developed algorithms.

scholarly journals N-Linked Glycopeptide Identification Based on Open Mass Spectral Library Search

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Zhiwu An ◽  
Qingbo Shu ◽  
Hao Lv ◽  
Lian Shu ◽  
Jifeng Wang ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Human Cancer ◽  
Cancer Cell Line ◽  
Peptide Identification ◽  
High Energy ◽  
Mass Spectral Library ◽  
Spectral Library ◽  
Data Set ◽  
Library Search ◽  
Mass Spectral

Confident characterization of intact glycopeptides is a challenging task in mass spectrometry-based glycoproteomics due to microheterogeneity of glycosylation, complexity of glycans, and insufficient fragmentation of peptide bones. Open mass spectral library search is a promising computational approach to peptide identification, but its potential in the identification of glycopeptides has not been fully explored. Here we present pMatchGlyco, a new spectral library search tool for intact N-linked glycopeptide identification using high-energy collisional dissociation (HCD) tandem mass spectrometry (MS/MS) data. In pMatchGlyco, (1) MS/MS spectra of deglycopeptides are used to create spectral library, (2) MS/MS spectra of glycopeptides are matched to the spectra in library in an open (precursor tolerant) manner and the glycans are inferred, and (3) a false discovery rate is estimated for top-scored matches above a threshold. The efficiency and reliability of pMatchGlyco were demonstrated on a data set of mixture sample of six standard glycoproteins and a complex glycoprotein data set generated from human cancer cell line OVCAR3.

scholarly journals Synthesis and potential cytotoxic activity of some new benzoxazoles, imidazoles, benzimidazoles and tetrazoles

2013 ◽  
Vol 63 (2) ◽  
pp. 253-264 ◽  
Author(s):  
Subramaniyan Arulmurugan ◽  
Helen P. Kavitha
Keyword(s):  
Breast Cancer ◽  
Mass Spectrometry ◽  
Colon Cancer ◽  
Heterocyclic Compounds ◽  
Human Cancer ◽  
Assay Method ◽  
Human Cancer Cell ◽  
Human Cancer Cell Lines ◽  
Ht 29 ◽  
Mcf 7

2 The present work deals with the synthesis of some novel heterocyclic compounds such as benzoxazoles , 7, 13 and 19, imidazoles 3, 8, 14 and 20, benzimidazoles 4, 9, 15 and 21, and tetrazoles 10, 16, and 22. The synthesized compounds were characterized by IR, 1H NMR, mass spectrometry and elemental analysis. The compounds were evaluated for cytotoxicity against human cancer cell lines such as MCF-7 (breast cancer) and HT-29 (colon cancer) by the MTT assay method. Among the tested compounds, 4,4’-sulfonylbis(N-(2-(1H-benzo[d]imidazol- -2-yl)ethyl)aniline (9), N-bis(2-(benzo[d]oxazol-2-yl)-ethyl)- 6-phenyl-1,3,5-triazine-2,4-diamine (13), N-bis(2-(1H-benzo[ d]imidazol-2-yl)ethyl)-6-phenyl-1,3,5-triazine-2,4-diamine (15) and N-tris(2-1H-benzo[d]imidazol-2-yl)ethyl)- 1,3,5-triazine-2,4,6-triamine (21) showed potent cytotoxicity.

scholarly journals Two New Taxane Diterpenoids From Taxus baccata

2020 ◽  
Vol 15 (9) ◽  
pp. 1934578X2095328
Author(s):  
Qi Ding ◽  
Dong-Mei Fang ◽  
Xiao-Huan Li ◽  
Feng Gao
Keyword(s):  
Mass Spectrometry ◽  
Human Cancer ◽  
Ionization Mass ◽  
Taxus Baccata ◽  
Human Cancer Cell ◽  
Human Cancer Cell Lines ◽  
Nuclear Magnetic Resonance Spectra ◽  
Taxane Diterpenoids ◽  
Taxane Diterpenoid ◽  
Mcf 7

Two new diterpenoids named 13-oxo-wollifoliane-10,15-olide (1) and 19-acetoxy-7,9,10-deacetyl-baccatin VI (2), along with 14 known taxanes (3-16), were isolated from Taxus baccata. The structures of these compounds were elucidated by 1-dimensional and 2-dimensional nuclear magnetic resonance spectra, high-resolution electrospray ionization-mass spectrometry, and infrared spectroscopy. Structurally, 13-oxo-wollifoliane-10,15-olide (1) is the first taxane diterpenoid possessing an unusual carbonyl group at the C-13 position of the 11(15→1),11(10→9)bis- abeo-taxane structure (5/6/6/6/4 skeleton), and 19-acetoxy-7,9,10-deacetyl-baccatin VI (2) is a new compound containing an acetoxy group at the C-19 position of 6/8/6/4-taxane. Among the 14 known taxane compounds 3-16, compounds 7 and 9 were first isolated and reported from T. baccata. Several compounds (3-16) were evaluated for cytotoxicity against MCF-7 and HCT116 human cancer cell lines, but none of them showed considerable cytotoxic activity.

scholarly journals Tetracyclines Modify Translation By Targeting Key Human rRNA Substructures

2018 ◽  
Author(s):  
Jonathan D. Mortison ◽  
Monica Schenone ◽  
Jacob A. Myers ◽  
Ziyang Zhang ◽  
Linfeng Chen ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Stress Response ◽  
Binding Sites ◽  
Human Cancer ◽  
Antimicrobial Properties ◽  
Human Cancer Cell ◽  
Quantitative Mass Spectrometry ◽  
Human Cancer Cell Lines ◽  
Nucleotide Resolution ◽  
Ribosomal Translation

SUMMARYApart from their antimicrobial properties, tetracyclines demonstrate clinically validated effects in the amelioration of pathological inflammation and human cancer. Delineation of the target(s) and mechanism(s) responsible for these effects, however, has remained elusive. Here, employing quantitative mass spectrometry-based proteomics, we identified human 80S ribosomes as targets of the tetracyclines Col-3 and doxycycline. We then developed in cell click selective crosslinking with RNA sequence profiling (icCL-Seq) to map binding sites for these tetracyclines on key human rRNA substructures at nucleotide resolution. Importantly, we found that structurally and phenotypically variant tetracycline analogs could chemically discriminate these rRNA binding sites. We also found that tetracyclines both subtly modify human ribosomal translation and selectively activate the cellular integrated stress response (ISR). Together, the data reveal that targeting of specific rRNA substructures, activation of the ISR, and inhibition of translation are correlated with the anti-proliferative properties of tetracyclines in human cancer cell lines.

Identification of Novel Sesamol Dimers with Unusual Methylenedioxy Ring-Opening Skeleton and Evaluation of Their Antioxidant and Cytotoxic Activities

2020 ◽  
Vol 16 (8) ◽  
pp. 1166-1173
Author(s):  
Sudtha Murthy ◽  
Ummi H.A.M. Hazli ◽  
Kin W. Kong ◽  
Chun-Wai Mai ◽  
Chee-Onn Leong ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Cell Lines ◽  
Ring Opening ◽  
Antioxidant Activities ◽  
Human Cancer ◽  
Oxidation Products ◽  
Cytotoxic Activities ◽  
Human Cancer Cell ◽  
X Ray ◽  
Human Cancer Cell Lines

Background: Sesamol is a widely used antioxidant for the food and pharmaceutical industries. The oxidation products of this compound may be accumulated in foods or ingested. Little is known about its effect on human health. Objective: It is of great interest to identify the oxidation products of sesamol that may be beneficial to humans. This study was undertaken to identify the oxidation products of sesamol and investigate their antioxidant and cytotoxic activities. Materials and Methods: Using the ferricyanide oxidation approach, four oxidation products of sesamol (2, 3, 20 & 21) have been identified. Structural elucidation of these compounds was established on the basis of their detailed NMR spectroscopic analysis, mass spectrometry and x-ray crystallography. Additionally, a formation mechanism of compound 20 was proposed based on high-resolution mass spectrometry-fragmentation method. The antioxidant activities of these compounds were determined by the DPPH, FRAP, and ABTS assays. The in vitro antiproliferative activity of these compounds was evaluated against a panel of human cancer cell lines as well as non-cancerous cells. Results: Two oxidation products of sesamol were found to contain an unusual methylenedioxy ring-opening skeleton, as evidenced by spectroscopic and x-ray crystallographic data. Among all compounds, 20 displayed impressive antiproliferative activities against a panel of human cancer cell lines yet remained non-toxic to noncancerous cells. The antioxidant activities of compound 20 are significantly weaker than sesamol as determined by the DPPH, FRAP, and ABTS assays. Conclusion:: The oxidation products of sesamol could be a valuable source of bioactive molecules. Compound 20 may be used as a potential lead molecule for cancer studies.

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