Xavier Barbeau

Xavier Barbeau
Laval University | ULAVAL · Department of Chemistry

About

52
Publications
3,782
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
565
Citations
Citations since 2017
31 Research Items
484 Citations
2017201820192020202120222023020406080100
2017201820192020202120222023020406080100
2017201820192020202120222023020406080100
2017201820192020202120222023020406080100

Publications

Publications (52)
Article
Steroid sulfatase (STS) is an important enzyme regulating the conversion of sulfated steroids into their active hydroxylated forms. Notably, the inhibition of STS has been shown to decrease the levels of active estrogens and was translated into clinical trials for the treatment of breast cancer. Based on quantitative structure-activity relationship...
Article
Full-text available
The delivery of biologic cargoes to airway epithelial cells is challenging due to the formidable barriers imposed by its specialized and differentiated cells. Among cargoes, recombinant proteins offer therapeutic promise but the lack of effective delivery methods limits their development. Here, we achieve protein and SpCas9 or AsCas12a ribonucleopr...
Article
Herein we report the anti-inflammatory activity of lobaric acid and pseudodepsidones isolated from the nordic lichen Stereocaulon paschale. Lobaric acid (1) and three compounds (2, 7 and 9) were found to inhibit the NF-κB activation and the secretion of pro-inflammatory cytokines (IL-1β and TNF-α) in LPS-stimulated macrophages. Inhibition and docki...
Article
17β-Hydroxysteroid dehydrogenase type 1 (17β-HSD1) is a promising therapeutic target known to play a pivotal role in the progression of estrogen-dependent diseases such as breast cancer, and endometriosis. This enzyme is responsible for the last step in the biosynthesis of the most potent estrogen, estradiol (E2) and its inhibition would prevent th...
Article
Full-text available
Duchenne muscular dystrophy (DMD), a severe hereditary disease affecting 1 in 3,500 boys, mainly results from the deletion of exon(s), leading to a reading frameshift of the DMD gene that abrogates dystrophin protein synthesis. Pairs of sgRNAs for the Cas9 of Staphylococcus aureus were meticulously chosen to restore a normal reading frame and also...
Preprint
Full-text available
Duchenne Muscular Dystrophy (DMD), a severe hereditary disease, affecting 1 boy out of 3500, mainly results from the deletion of one or more exons leading to a reading frame shift of the DMD gene that abrogates dystrophin protein synthesis. We used the Cas9 of Staphylococcus aureus (SaCas9) to edit the human DMD gene. Pairs of sgRNAs were meticulou...
Article
Full-text available
Delivery of recombinant proteins to therapeutic cells is limited by a lack of efficient methods. This hinders the use of transcription factors or Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) ribonucleoproteins to develop cell therapies. Here, we report a soluble peptide designed for the direct delivery of proteins to mammalian...
Data
Peptide sequences listing and features. (DOCX)
Data
Nuclear localization of Cas9-NLS and Cpf1-NLS proteins after 6His-CM18-PTD4-mediated delivery in HeLa cells. 6His-CM18-PTD4 (10 μM) and CRISPR Cas9-NLS or CRISPR Cpf1-NLS RNPs were co-incubated for 1 min with HeLa cells. Cells were fixed and permeabilized prior to immuno-labelling of Cas9 or Cpf1 with specific antibodies. Numerical values were obta...
Data
Size of cleavage product fragments from Fig 3. (DOCX)
Data
Fast and repeated GFP-NLS and HoxB4 delivery with 6His-CM18-PTD4 in THP1 cells. (A-B) Flow cytometry raw data of THP-1 cell viability depending size and coarseness (upper panels) and of GFP signal after GFP-NLS (10 μM) delivery (bottom panels). (A) Different concentrations of 6His-CM18-PTD4 (10 μM) and GFP-NLS (10 μM) were co-incubated for 15 secs...
Data
Secondary structures prediction of PTD4, CM18, CM18-PTD4 and 6His-CM18-PTD4 peptides. (DOCX)
Data
One-minute co-incubation with 6His-CM18-PTD4 results in efficient and safe delivery of GFP-NLS in multiple mammalian cells. (A) Flow cytometry raw data of HeLa cell viability depending size and coarseness (upper panels) and of GFP signal after GFP-NLS (10 μM) delivery (bottom panels). CM18 /PTD4 peptides analogues (10 μM) and GFP-NLS (10 μM) were c...
Data
6His-CM18-PTD4 mediates endosomal membrane disruption at low concentration. (A) Flow cytometry raw data of HeLa cell viability depending size and coarseness (upper panels) and of GFP signal after GFP-NLS (10 μM) delivery (bottom panels). 6His-CM18-PTD4 (10 μM) and GFP-NLS (10 μM) were co-incubated with HeLa cells for 1 min at 37°C and 4°C or in pre...
Data
Correlation between amphiphilic properties of 6His-CM18-PTD4 and protein delivery efficiency. (A) Helical wheel projections of the PTD4, CM18, CM18-PTD4 and 6His-CM18-PTD4 peptides (Top view) were determined and adapted to this article with the free http://rzlab.ucr.edu/scripts/wheel/wheel.cgi software source code. This software measures the hydrop...
Article
Understanding the function of cellular systems requires describing how proteins assemble with each other into transient and stable complexes and to determine their spatial relationships. Among the tools available to perform these analyses on a large scale is Protein-fragment Complementation Assay based on the dihydrofolate reductase (DHFR PCA). Her...
Article
The ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (NPP1) was recently shown to promote mineralization of the aortic valve, hence, its inhibition represents a significant target. A quinazoline-4-piperidine sulfamide compound (QPS1) has been described as a specific and non-competitive inhibitor of NPP1. We report herein the synthesis and in vit...
Article
Full-text available
Macrocycles are cyclic macromolecules that have gained an increased interest in drug development. To our knowledge, the current bioinformatics tools that are available to investigate and predict macrocycles 3D conformations are limited in their availability. In this paper, we introduce ConfBuster, a suite of tools written in Python with the goal of...
Article
Full-text available
Understanding the function of cellular systems requires describing how proteins assemble with each other into transient and stable complexes and to determine their spatial relationships. Among the tools available to perform these analyses on a large scale is the Protein-fragment Complementation Assay based on the dihydrofolate reductase (DHFR PCA)....
Article
17β-Hydroxysteroid dehydrogenase type 1 (17β-HSD1) is involved in the biosynthesis of estradiol, the major bioactive endogenous estrogen in mammals, and constitutes an interesting therapeutic target for estrogen-dependent diseases. A steroidal derivative, 3-{[(16β,17β)-3-(2-bromoethyl)-17-hydroxyestra-1,3,5(10)-trien-16-yl]methyl} benzamide (PBRM),...
Article
The ectonucleotide phosphodiesterase/pyrophosphatase-1 (NPP1) is a type II transmembrane glycoprotein that regulates extracellular inorganic purine nucleotide and inorganic diphosphate levels through the hydrolysis of ATP into AMP and diphosphate. NPP1 is a promising drug target as it plays a role in several disorders. In the present work, we repor...
Article
Full-text available
We describe an efficient epoxidation process leading to chiral epoxyketones using the reusable homo-oligopeptide poly-l-leucine (PLL) in pure water, without any organic co-solvent. A range of substituted epoxyketones can be accessed with good conversions and high enantioselectivities. Based on the experimental results and computational studies, we...
Article
Emergence of pan neuraminidase inhibitor (NAI)-resistant variants constitutes a serious clinical concern. An influenza A(H1N1)pdm09 variant containing the I427T/Q313R neuraminidase (NA) substitutions was previously identified in a surveillance study. Although these changes are not part of the NA active site, the variant showed reduced susceptibilit...
Article
Full-text available
We synthesised a library of cis- and trans-cyclic dipeptides and evaluated their efficacy as catalysts in the asymmetric Weitz-Scheffer epoxidation of trans-chalcone. A thorough investigation relying on structure-activity studies and computational studies provided insights into the mechanism of the process. Our results revealed some structural feat...
Article
Steroid sulfatase (STS), the enzyme which converts inactive sulfated steroid precursors into active hormones, is a promising therapeutic target for the treatment of estrogen-sensitive breast cancer. We report herein the synthesis and in vitro study of dual-action STS inhibitors with selective estrogen-receptor modulator (SERM) effects. A library of...
Article
Aeromonas salmonicida subsp. salmonicida is a fish pathogen known to have a rich plasmidome. In the present study, we discovered an isolate of this bacterium bearing an additional unidentified small plasmid. After having sequenced the DNA of that isolate by next-generation sequencing, it appeared that the new small plasmid is a ColE1-type replicon...
Article
Full-text available
The CRISPR/Cas9 system is a great revolution in biology. This technology allows the modification of genes in vitro and in vivo in a wide variety of living organisms. In most Duchenne muscular dystrophy (DMD) patients, expression of dystrophin (DYS) protein is disrupted because exon deletions result in a frame shift. We present here the CRISPR-induc...
Article
The chemical synthesis of four stereoisomers (compounds 5a-5d) of 16β-(m-carbamoylbenzyl)-estradiol, a potent reversible inhibitor of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1), and two intermediates (compounds 3a and 3b) was performed. Assignment of all nuclear magnetic resonance signals confirmed the stereochemistry at positions 13, 16 an...
Article
Full-text available
With the objective of developing novel chiral ligands, we report an efficient strategy to prepare chiral N,. N-dimethyl-1,4-piperazines, six-member heterocyclic molecules that possess metal binding features. We prepared and characterized 18 piperazines, and evaluated their ability to complex different mono- and divalent metals, using a rapid picrat...
Article
Full-text available
Roseobacter denitrificans is a member of the widespread marine Roseobacter genus. We report the first characterization of a truncated hemoglobin from R. denitrificans (Rd. trHb) that was purified in the heme-bound form from heterologous expression of the protein in Escherichia coli. Rd. trHb exhibits predominantly alpha-helical secondary structure...
Article
Ectonucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) is an ectoenzyme, which plays a role in several disorders including calcific aortic valve disease (CAVD). So far, compounds that have been developed as inhibitors of NPP1 lack potency and specificity. Quinazolin-4-piperidine sulfamides (QPS) have been described as potent inhibitors of NPP1....
Article
Full-text available
For tRNA-dependent protein biosynthesis, amino acids are first activated by aminoacyl-tRNA synthetases (aaRSs) yielding the reaction intermediates aminoacyl-AMP (aa-AMP). Stable analogues of aa-AMP, such as aminoacyl-sulfamoyl-adenosines, inhibit their cognate aaRSs. Glutamyl-sulfamoyl-adenosine (Glu-AMS) is the best known inhibitor of Escherichia...
Article
BACKGROUND: Ectonucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) is an ectoenzyme, which plays a role into several disorders including calcific aortic valve disease (CAVD). So far, compounds that have been developed as inhibitors of NPP1 lack of potency and specificity. Quinazolin-4-piperidin-4-methyl sulfamide (QPS) derivatives have been desc...
Article
17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) is thought to play a pivotal role in the progression of estrogen-sensitive breast cancer by transforming estrone (E1) into estradiol (E2). We designed three successive series of E2-derivatives at position C3 of the potent inhibitor 16β-(m-carbamoylbenzyl)-E2 to remove its unwanted estrogenic activi...
Article
The bacterium Aeromonas salmonicida, a fish pathogen, uses the type three secretion system (TTSS) to inject effector proteins into host cells to promote the infection. The study of the genome of A. salmonicida has revealed the existence of Ati2, a potential TTSS effector protein. In the present study, a structure-function analysis of Ati2 has been...
Article
An addition/elimination reaction of organolithium reagents to silylated beta,beta-difluorostyrene derivatives followed by a bromination/desilicobromination reaction provides a simple and effective synthetic approach to a wide range of bromofluoroalkenes (up to >97/3). In addition, the bromofluoroalkenes can be used in Pd-catalyzed transformations g...

Network

Cited By

Projects

Project (1)
Project
Our objective is to obtain a potent steroid sulfatase inhibitor with SERM properties to treat estrogen and androgen dependant diseases like breast and prostate cancers, and endometriosis as well.