A co-formulation of interferons alpha2b and gamma distinctively targets cell cycle in the glioblastoma-derived cell line U-87MG.

Background: HeberFERON is a co-formulation of α2b and γ interferons, based on their synergism, which has shown its clinical superiority over individual interferons in basal cell carcinomas. In glioblastoma (GBM), HeberFERON has displayed promising preclinical and clinical results. This led us to design a microarray experiment aimed at identifying the molecular mechanisms involved in the distinctive effect of HeberFERON compared to the individual interferons in U-87MG model.

Synergic effect of anticancer peptide CIGB-552 and Cisplatin in lung cancer models.

Background: The antitumor peptide CIGB-552 is a new targeted anticancer therapy which molecular mechanism is associated with the inhibition of the transcription factor NF-kB, mediated by COMMD1 protein stabilization. In this study, we examined the antiproliferative capacity of CIGB-552 in combination with chemotherapeutic agents in lung cancer models.

Methods And Results: We combined of CIGB-552 and the antineoplastic agent Cisplatin (CDDP) in concomitant and pre-treatment scenary in a dose matrix approach.

Targeting CK2 mediated signaling to impair/tackle SARS-CoV-2 infection: a computational biology approach.

Background: Similarities in the hijacking mechanisms used by SARS-CoV-2 and several types of cancer, suggest the repurposing of cancer drugs to treat Covid-19. CK2 kinase antagonists have been proposed for cancer treatment. A recent study in cells infected with SARS-CoV-2 found a significant CK2 kinase activity, and the use of a CK2 inhibitor showed antiviral responses.

A self-consistent probabilistic formulation for inference of interactions.

Large molecular interaction networks are nowadays assembled in biomedical researches along with important technological advances. Diverse interaction measures, for which input solely consisting of the incidence of causal-factors, with the corresponding outcome of an inquired effect, are formulated without an obvious mathematical unity. Consequently, conceptual and practical ambivalences arise.

Proteomic Study to Survey the CIGB-552 Antitumor Effect.

CIGB-552 is a cell-penetrating peptide that exerts in vitro and in vivo antitumor effect on cancer cells. In the present work, the mechanism involved in such anticancer activity was studied using chemical proteomics and expression-based proteomics in culture cancer cell lines. CIGB-552 interacts with at least 55 proteins, as determined by chemical proteomics.

Synergistic interactions of the anti-casein kinase 2 CIGB-300 peptide and chemotherapeutic agents in lung and cervical preclinical cancer models.

CIGB-300 is a novel clinical-stage synthetic peptide that impairs the casein kinase 2 (CK2)-mediated phosphorylation of B23/nucleophosmin in different experimental settings and cancer models. As a single agent, CIGB-300 induces apoptosis and and modulates an array of proteins that are mainly involved in drug resistance, cell proliferation and apoptosis, as determined by proteomic analysis. However, the clinical oncology practice and cumulative knowledge on tumor biology suggest that drug combinations are more likely to cope with tumor complexity compared to single agents.

Computation of isotopic peak center-mass distribution by Fourier transform.

We derive a new efficient algorithm for the computation of the isotopic peak center-mass distribution of a molecule. With the use of Fourier transform techniques, the algorithm accurately computes the total abundance and average mass of all the isotopic species with the same number of nucleons. We evaluate the performance of the method with 10 benchmark proteins and other molecules; results are compared with BRAIN, a recently reported polynomial method.

Introducing an Asp-Pro linker in the synthesis of random one-bead-one-compound hexapeptide libraries compatible with ESI-MS analysis.

A random hexapeptide library (one-bead-one-compound), containing sixteen amino acids (16(6) different sequences) was synthesized on a Tentagel resin previously modified with a dipeptide linker (Asp-Pro). This peptide bond is highly susceptible to cleavage under mild acidic conditions in a salt-free solution prepared with H(2)(16)O/H(2)(18)O (60/40% v/v). In the hydrolysis, hexapeptides are released with an additional Asp residue partially labeled with (18)O at the C-terminus.

Selective isolation of multiply charged peptides: a confident strategy for protein identification using a linear trap quadrupole mass spectrometer.

In this work, a method devised for the selective isolation of multiply-charged peptide applied to a complex protein mixture was evaluated for the first time using a mass spectrometer with low resolution (LTQ). In this procedure, all primary amino groups of tryptic peptides derived from human Liver tissue interstitial fluid (TIF) are blocked, restricting their positive charge, at acidic pH, to the presence of histidine and arginine residues. After strong cation exchange chromatography, multiply-charged peptides (#R+#H > 1) are retained in the column and separated with high selectivity from singly (#R+#H = 1) and neutral peptides (#R +#H = 0) which are collected together in the flow-through.

A methodology based on molecular interactions and pathways to find candidate genes associated to diseases: its application to schizophrenia and Alzheimer's disease.

Experimental techniques for the identification of genes associated with diseases are expensive and have certain limitations. In this scenario, computational methods are useful tools to identify lists of promising genes for further experimental verification. This paper describes a flexible methodology for the in silico prediction of genes associated with diseases combining the use of available tools for gene enrichment analysis, gene network generation and gene prioritization.

Charge state-selective separation of peptides by reversible modification of amino groups and strong cation-exchange chromatography: evaluation in proteomic studies using peptide-centric database searches.

Here we describe an integrated approach for the selective separation of peptides from complex mixtures using strong cation-exchange chromatography. The procedure exploits the charge differences produced by reversible modification of primary amino groups in peptides, enabling their separation into three major fractions: 1) neutral peptides 2) peptides with one positive charge and 3) peptides with 2 or more positive charges. The procedure demonstrated an excellent selectivity which allowed restricted MS/MS ion searches with peptide-centric databases.

Mass spectrum patterns of 18O-tagged peptides labeled by enzyme-catalyzed oxygen exchange.

(18)O-labeling of peptides is a technique widely and routinely applied in the protein chemistry laboratories. The rate of (18)O incorporation at the carboxyl terminus of peptides via enzyme-catalyzed oxygen exchange fluctuates from peptide to peptide. This fluctuation is mostly attributed to enzyme-substrate different affinity.

Selective isolation-detection of two different positively charged peptides groups by strong cation exchange chromatography and matrix-assisted laser desorption/ionization mass spectrometry: application to proteomics studies.

We report here a procedure for the independent analysis of two groups of peptides by liquid chromatography-matrix-assisted laser desorption/ionization mass spectrometry (LC-MALDI MS/MS), using a selective isolation-detection procedure. In this procedure all primary amino groups of tryptic peptides derived from mouse liver proteins are blocked, restricting their positive charge, at acidic pH, to the presence of histidine and arginine residues. After strong cation exchange chromatography, multiply charged peptides (R + H > 1) are retained on the column and separated with high selectivity from singly (R + H = 1) and neutral peptides (R + H = 0) which are together collected in the flow-through.

Proteomic profile regulated by the anticancer peptide CIGB-300 in non-small cell lung cancer (NSCLC) cells.

CIGB-300 is a proapoptotic peptide-based drug that abrogates the CK2-mediated phosphorylation. This peptide has antineoplastic effect on lung cancer cells in vitro and in vivo. To understand the mechanisms involved on such anticancer activity, the NCI-H125 cell line proteomic profile after short-term incubation (45 min) with CIGB-300 was investigated.

Computation of the isotopic distribution in two dimensions.

A new algorithm for the calculation of the isotopic distribution is described here. The extreme levels of detail, the coarser structures (approximately 1 Da) and the sharper irregular details (approximately millidaltons), get split in separate dimensions. Consequently, dense sampling can be concentrated in the close informative surrounding of the isotopic peaks.

BisoGenet: a new tool for gene network building, visualization and analysis.

Background: The increasing availability and diversity of omics data in the post-genomic era offers new perspectives in most areas of biomedical research. Graph-based biological networks models capture the topology of the functional relationships between molecular entities such as gene, protein and small compounds and provide a suitable framework for integrating and analyzing omics-data. The development of software tools capable of integrating data from different sources and to provide flexible methods to reconstruct, represent and analyze topological networks is an active field of research in bioinformatics.

Efficient packing Fourier-transform approach for ultrahigh resolution isotopic distribution calculations.

Fine isotopic structure patterns resolvable by ultrahigh-resolution mass spectrometers are diagnostic of the elemental composition of moderately large compounds. Despite the proven performance of Fourier transforms algorithms to calculate accurate high resolution isotopic distribution, its application to finer ultrahigh resolving power exhibits limited performance. Fast Fourier transforms algorithm requires sampling the relevant range at equally spaced mass values, but ultrahigh resolution mass spectrum displays highly localized complex patterns (peaks) separated in between by relatively large unstructured intervals.

Proteomics based on peptide fractionation by SDS-free PAGE.

Here we demonstrate the usefulness of peptide fractionation by SDS-free polyacrylamide gel electrophoresis and its applicability to proteomics studies. In the absence of SDS, the driving force for the electrophoretic migration toward the anode is supplied by negatively charged acidic amino acid residues and other residues as phosphate, sulfate and sialic acid, while the resulting mobility depends on both the charge and the molecular mass of the peptides. A straightforward method was achieved for SDS-PAGE of proteins, enzyme digestion, peptide transfer and fractionation by SDS-free PAGE, which was named dual-fractionation polyacrylamide gel electrophoresis (DF-PAGE).

HLA class I polymorphism in the Cuban population.

The extreme polymorphism found at some of the human leukocyte antigen (HLA) system loci makes it an invaluable tool for population genetic analyses. In the present study the genetic polymorphism of the Cuban population was estimated at HLA-A, -B, and -Cw loci by DNA typing. HLA class I allele and haplotype diversity were determined in 390 unrelated Cuban individuals (188 whites and 202 mulattos) from all over the country.

Selective isolation of multiple positively charged peptides for 2-DE-free quantitative proteomics.

A method for quantitative proteomic analysis based on the selective isolation of multiply charged peptides (RH peptides) containing arginine and histidine residues is described. Two pools of proteins are digested in tandem with lysyl-endopeptidase and trypsin and the primary amino groups of proteolytic peptides are separately labeled with d3- and d0-acetic anhydride. This reaction has a dual purpose: (i) to allow the relative protein quantification in two different conditions and (ii) to restrict the positive charges of peptides to the presence of arginine and histidine.

Selective isolation of lysine-free tryptic peptides delimited by arginine residues: A new tool for proteome analysis.

Tryptic digestion of biotinylated Lys-C peptides followed by affinity chromatography allows the selective isolation of lysine-free tryptic peptides delimited by arginine residues (RRnK peptides). In silico analysis revealed that RRnK peptides represent 87% of the whole proteomes and their specific isolation simplifies the complex peptide mixture (5 peptides per protein). The good recoveries and high selectivity obtained in the isolation of RRnK peptides anticipate the applicability of this method in 2DE-free quantitative proteome analyses.

SCAPE: a new tool for the Selective CApture of PEptides in protein identification.

A method for the selective capture and analysis of peptides containing neither histidine nor arginine is evaluated. It is based on the reversible modification of alpha- and epsilon-amino groups of peptides and the relatively easy separation of charged and noncharged peptides by cation exchange chromatography. The simplicity of the method and the results obtained in silico and with standard proteins, anticipate the utility of the SCAPE approach for proteome analyses.

Automated interpretation of mass spectra of complex mixtures by matching of isotope peak distributions.

Mass spectrometry is now firmly established as a powerful technique for the identification and characterization of proteins when used in conjunction with sequence databases. Various approaches involving stable-isotope labeling have been developed for quantitative comparisons between paired samples in proteomic expression analysis by mass spectrometry. However, interpretation of such mass spectra is far from being fully automated, mainly due to the difficulty of analyzing complex patterns resulting from the overlap of multiple peaks arising from the assortment of natural isotopes.

Isotopica: a tool for the calculation and viewing of complex isotopic envelopes.

The web application Isotopica has been developed as an aid to the interpretation of ions that contain naturally occurring isotopes in a mass spectrum. It allows the calculation of mass values and isotopic distributions based on molecular formulas, peptides/proteins, DNA/RNA, carbohydrate sequences or combinations thereof. In addition, Isotopica takes modifications of the input molecule into consideration using a simple and flexible language as a straightforward extension of the molecular formula syntax.