Sophie Beauchemin
Université de Sherbrooke
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Publication
Featured researches published by Sophie Beauchemin.
Bioorganic & Medicinal Chemistry Letters | 2008
Eric Marsault; Hamid R. Hoveyda; René Gagnon; Mark L. Peterson; Martin Vezina; Carl Saint-Louis; Annick Landry; Jean François Pinault; Luc Ouellet; Sophie Beauchemin; Sylvie Beaubien; Axel P. Mathieu; Kamel Benakli; Zhigang Wang; Martin Brassard; David Lonergan; François Bilodeau; Mahesh Ramaseshan; Nadia Fortin; Ruoxi Lan; Shigui Li; Fabrice Galaud; Véronique Plourde; Manon Champagne; Annie Doucet; Patrick Bherer; Maude Gauthier; Gilles Olsen; Gérald Villeneuve; Shridhar Bhat
A new method for solid phase parallel synthesis of chemically and conformationally diverse macrocyclic peptidomimetics is reported. A key feature of the method is access to broad chemical and conformational diversity. Synthesis and mechanistic studies on the macrocyclization step are reported.
Journal of Medicinal Chemistry | 2014
Gagnon H; Sophie Beauchemin; Anna Kwiatkowska; Frédéric Couture; D'Anjou F; Christine Levesque; Dufour F; Desbiens Ar; Vaillancourt R; Bernard S; Roxane Desjardins; Malouin F; Yves L. Dory; Robert W. Day
Proprotein convertases (PCs) are crucial in the processing and entry of viral or bacterial protein precursors and confer increased infectivity of pathogens bearing a PC activation site, which results in increased symptom severity and lethality. Previously, we developed a nanomolar peptide inhibitor of PCs to prevent PC activation of infectious agents. Herein, we describe a peptidomimetic approach that increases the stability of this inhibitor for use in vivo to prevent systemic infections and cellular damage, such as that caused by influenza H5N1 and Shiga toxin. The addition of azaβ(3)-amino acids to both termini of the peptide successfully prevented influenza hemagglutinin 5 fusogenicity and Shiga toxin Vero toxicity in cell-based assays. The results from a cell-based model using stable shRNA-induced proprotein convertase knockdown indicate that only furin is the major proprotein convertase required for HA5 cleavage.
Journal of Medicinal Chemistry | 2014
Anna Kwiatkowska; Frédéric Couture; Christine Levesque; Kévin Ly; Roxane Desjardins; Sophie Beauchemin; Adam Prahl; Bernard Lammek; Witold Neugebauer; Yves L. Dory; Robert W. Day
PACE4 plays an important role in the progression of prostate cancer and is an attractive target for the development of novel inhibitor-based tumor therapies. We previously reported the design and synthesis of a novel, potent, and relatively selective PACE4 inhibitor known as a Multi-Leu (ML) peptide. In the present work, we examined the ML peptide through detailed structure-activity relationship studies. A variety of ML-peptide analogues modified at the P8-P5 positions with leucine isomers (Nle, DLeu, and DNle) or substituted at the P1 position with arginine mimetics were tested for their inhibitory activity, specificity, stability, and antiproliferative effect. By incorporating d isomers at the P8 position or a decarboxylated arginine mimetic, we obtained analogues with an improved stability profile and excellent antiproliferative properties. The DLeu or DNle residue also has improved specificity toward PACE4, whereas specificity was reduced for a peptide modified with the arginine mimetic, such as 4-amidinobenzylamide.
Tetrahedron | 1996
Jean-Marc Chapuzet; Sophie Beauchemin; Benoit Daoust; Jean Lessard
Abstract The methanolysis of allylic alcohols, benzylic tertiary alcohols and epoxides in the presence of a catalytic amount of ceric ammonium nitrate (CAN) is shown to be catalysed by protons generated from the oxidation of methanol. This reaction is also catalysed by Lewis acids.
ChemMedChem | 2016
Anna Kwiatkowska; Frédéric Couture; Christine Levesque; Kévin Ly; Sophie Beauchemin; Roxane Desjardins; Witold Neugebauer; Yves L. Dory; Robert Day
PACE4 plays important roles in prostate cancer cell proliferation. The inhibition of this enzyme has been shown to slow prostate cancer progression and is emerging as a promising therapeutic strategy. In previous work, we developed a highly potent and selective PACE4 inhibitor, the multi‐Leu (ML) peptide, an octapeptide with the sequence Ac‐LLLLRVKR‐NH2. Here, with the objective of developing a useful compound for in vivo administration, we investigate the effect of N‐terminal modifications. The inhibitory activity, toxicity, stability, and cell penetration properties of the resulting analogues were studied and compared to the unmodified inhibitor. Our results show that the incorporation of a polyethylene glycol (PEG) moiety leads to a loss of antiproliferative activity, whereas the attachment of a lipid chain preserves or improves it. However, the lipidated peptides are significantly more toxic when compared with their unmodified counterparts. Therefore, the best results were achieved not by the N‐terminal extension but by the protection of both ends with the d‐Leu residue and 4‐amidinobenzylamide, which yielded the most stable inhibitor, with an excellent activity and toxicity profile.
Biopolymers | 2018
Dominique Bella Ndong; Véronique Blais; Brian J. Holleran; Arnaud Proteau-Gagné; Isabelle Cantin-Savoie; William Robert; Jean-François Nadon; Sophie Beauchemin; Richard Leduc; Graciela Piñeyro; Brigitte Guérin; Louis Gendron; Yves L. Dory
Enkephalins are pentapeptidic endogenous ligands that regulate nociception by binding to mu (MOP) and delta (DOP) opioid receptors. To further explore the role of the leucine residue of Leu‐enkephalin, 12 peptidomimetic analogs were synthesized by systematically replacing this residue with non‐natural amino acids. The analogs were tested for their ability to bind DOP and MOP. We also investigated the potency of these analogs to inhibit cAMP production and to recruit β‐arrestin 2 via both receptors. We found that replacement of the leucine residue by substituted non‐natural amino acid derivatives of alanine, cycloleucine, or isoleucine was generally well tolerated. By contrast, substituting leucine with homoproline greatly reduced the affinity for DOP and, to a lesser extent, for MOP. Interestingly, when compared to Leu‐enkephalin, analogs containing either aza‐β‐homoleucine or cycloleucine showed a bias toward inhibition of cAMP production through the activation of DOP but not MOP. By contrast, derivatives containing 4,5‐dehydroleucine or d‐allo‐isoleucine conferred a bias toward β‐arrestin 2 at MOP, but not DOP. Our results suggest that position 5 in Leu‐enkephalin analogs can be further exploited to develop compounds with the potential to produce bias toward G protein or β‐arrestin 2.
Journal of Medicinal Chemistry | 2011
Hamid R. Hoveyda; Eric Marsault; René Gagnon; Axel P. Mathieu; Martin Vezina; Annick Landry; Zhigang Wang; Kamel Benakli; Sylvie Beaubien; Carl Saint-Louis; Martin Brassard; Jean François Pinault; Luc Ouellet; Shridhar Bhat; Mahesh Ramaseshan; Xiaowen Peng; Laurence Foucher; Sophie Beauchemin; Patrick Bherer; Daniel F. Veber; Mark L. Peterson; Graeme Fraser
Journal of Medicinal Chemistry | 2006
Eric Marsault; Hamid R. Hoveyda; Mark L. Peterson; Carl Saint-Louis; Annick Landry; Martin Vezina; Luc Ouellet; Zhigang Wang; Mahesh Ramaseshan; Sylvie Beaubien; Kamel Benakli; Sophie Beauchemin; Robert Deziel; Theo Peeters; Graeme Fraser
Archive | 2008
Hamid R. Hoveyda; Graeme Fraser; Kamel Benakli; Sophie Beauchemin; Martin Brassard; David J. Drutz; Eric Marsault; Luc Ouellet; Mark L. Peterson; Zhigang Wang
Archive | 2010
Hamid R. Hoveyda; Eric Marsault; Helmut Thomas; Graeme Fraser; Sylvie Beaubien; Axel P. Mathieu; Julien Beignet; Marc-André Bonin; Serge Phoenix; David J. Drutz; Mark L. Peterson; Sophie Beauchemin; Martin Brassard; Martin Vezina