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Papers by Françoise Debart
European Journal of Organic Chemistry, Sep 12, 2019
Viral RNA 2'-O-methyltransferases play a crucial role for luring the host cell innate antiviral r... more Viral RNA 2'-O-methyltransferases play a crucial role for luring the host cell innate antiviral response during a viral infection by catalyzing either the methylation of the 5'-end RNA cap-structure at 2'-OH of nucleoside N1 or by inducing internal 2'-O-methylation of adenosines within RNA sequence using S-adenosyl-L-methionine (SAM) as the methyl donor. Our goal is to synthetized bisubstrate SAM analogues mimicking the transition state of the 2'-O-methylation of the RNA in order to block viral 2'-O-methyltransferases and struggle against emerging viruses. Here we designed and synthesized five dinucleosides by connecting a 5'-thioadenosine representing the SAM to the 2'-OH of another adenosine unit mimicking the RNA substrate, via various sized sulfur-containing linkers such as alkylthioether linkers, sulfoxide or sulfone derivatives, or a disulfide bond.
HAL (Le Centre pour la Communication Scientifique Directe), 2011
HAL (Le Centre pour la Communication Scientifique Directe), 2010
Journal of Organic Chemistry, Jun 16, 2011
31 P NMR of all new compounds. HPLC profiles and MALDI-TOF spectra of synthesized oligonucleotide... more 31 P NMR of all new compounds. HPLC profiles and MALDI-TOF spectra of synthesized oligonucleotides. This material is available free of charge via the Internet at http://pubs.acs.org.
Nucleosides, Nucleotides & Nucleic Acids, Mar 31, 2001
HAL (Le Centre pour la Communication Scientifique Directe), 2012
International audienc
Organic and Biomolecular Chemistry, 2013
European Journal of Organic Chemistry, Dec 5, 2014
European Journal of Medicinal Chemistry
Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on ... more Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
Nucleic Acids Research
RNA 2′O-methylation is a ‘self’ epitranscriptomic modification allowing discrimination between ho... more RNA 2′O-methylation is a ‘self’ epitranscriptomic modification allowing discrimination between host and pathogen. Indeed, human immunodeficiency virus 1 (HIV-1) induces 2′O-methylation of its genome by recruiting the cellular FTSJ3 methyltransferase, thereby impairing detection by RIG-like receptors. Here, we show that RNA 2′O-methylations interfere with the antiviral activity of interferon-stimulated gene 20-kDa protein (ISG20). Biochemical experiments showed that ISG20-mediated degradation of 2′O-methylated RNA pauses two nucleotides upstream of and at the methylated residue. Structure-function analysis indicated that this inhibition is due to steric clash between ISG20 R53 and D90 residues and the 2′O-methylated nucleotide. We confirmed that hypomethylated HIV-1 genomes produced in FTSJ3-KO cells were more prone to in vitro degradation by ISG20 than those produced in cells expressing FTSJ3. Finally, we found that reverse-transcription of hypomethylated HIV-1 was impaired in T cel...
Nature Communications, 2015
The L protein of mononegaviruses harbours all catalytic activities for genome replication and tra... more The L protein of mononegaviruses harbours all catalytic activities for genome replication and transcription. It contains six conserved domains (CR-I to -VI; Fig. 1a). CR-III has been linked to polymerase and polyadenylation activity, CR-V to mRNA capping and CR-VI to cap methylation. However, how these activities are choreographed is poorly understood. Here we present the 2.2-Å X-ray structure and activities of CR-VI+, a portion of human Metapneumovirus L consisting of CR-VI and the poorly conserved region at its C terminus, the +domain. The CR-VI domain has a methyltransferase fold, which besides the typical S-adenosylmethionine-binding site (SAMP) also contains a novel pocket (NSP) that can accommodate a nucleoside. CR-VI lacks an obvious cap-binding site, and the SAMP-adjoining site holding the nucleotides undergoing methylation (SUBP) is unusually narrow because of the overhanging +domain. CR-VI+ sequentially methylates caps at their 2′O and N7 positions, and also displays nucle...
Collection Symposium Series, 2014
Nucleic acids symposium series, 1992
A convenient synthesis of a thymidine (T) nucleoside dimer (T-3'-CH2-O-NCH3-CH2-4'-T) 12 ... more A convenient synthesis of a thymidine (T) nucleoside dimer (T-3'-CH2-O-NCH3-CH2-4'-T) 12 has been accomplished via a nucleoside coupling reaction. An alternative synthesis of 3'-deoxy-3'-C-hydroxymethyl-thymidine is described. The new dimer and methodology is useful for the development of backbone-modified antisense oligonucleosides.
ChemInform, 2004
For Abstract see ChemInform Abstract in Full Text.
European Journal of Organic Chemistry, Sep 12, 2019
Viral RNA 2'-O-methyltransferases play a crucial role for luring the host cell innate antiviral r... more Viral RNA 2'-O-methyltransferases play a crucial role for luring the host cell innate antiviral response during a viral infection by catalyzing either the methylation of the 5'-end RNA cap-structure at 2'-OH of nucleoside N1 or by inducing internal 2'-O-methylation of adenosines within RNA sequence using S-adenosyl-L-methionine (SAM) as the methyl donor. Our goal is to synthetized bisubstrate SAM analogues mimicking the transition state of the 2'-O-methylation of the RNA in order to block viral 2'-O-methyltransferases and struggle against emerging viruses. Here we designed and synthesized five dinucleosides by connecting a 5'-thioadenosine representing the SAM to the 2'-OH of another adenosine unit mimicking the RNA substrate, via various sized sulfur-containing linkers such as alkylthioether linkers, sulfoxide or sulfone derivatives, or a disulfide bond.
HAL (Le Centre pour la Communication Scientifique Directe), 2011
HAL (Le Centre pour la Communication Scientifique Directe), 2010
Journal of Organic Chemistry, Jun 16, 2011
31 P NMR of all new compounds. HPLC profiles and MALDI-TOF spectra of synthesized oligonucleotide... more 31 P NMR of all new compounds. HPLC profiles and MALDI-TOF spectra of synthesized oligonucleotides. This material is available free of charge via the Internet at http://pubs.acs.org.
Nucleosides, Nucleotides & Nucleic Acids, Mar 31, 2001
HAL (Le Centre pour la Communication Scientifique Directe), 2012
International audienc
Organic and Biomolecular Chemistry, 2013
European Journal of Organic Chemistry, Dec 5, 2014
European Journal of Medicinal Chemistry
Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on ... more Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
Nucleic Acids Research
RNA 2′O-methylation is a ‘self’ epitranscriptomic modification allowing discrimination between ho... more RNA 2′O-methylation is a ‘self’ epitranscriptomic modification allowing discrimination between host and pathogen. Indeed, human immunodeficiency virus 1 (HIV-1) induces 2′O-methylation of its genome by recruiting the cellular FTSJ3 methyltransferase, thereby impairing detection by RIG-like receptors. Here, we show that RNA 2′O-methylations interfere with the antiviral activity of interferon-stimulated gene 20-kDa protein (ISG20). Biochemical experiments showed that ISG20-mediated degradation of 2′O-methylated RNA pauses two nucleotides upstream of and at the methylated residue. Structure-function analysis indicated that this inhibition is due to steric clash between ISG20 R53 and D90 residues and the 2′O-methylated nucleotide. We confirmed that hypomethylated HIV-1 genomes produced in FTSJ3-KO cells were more prone to in vitro degradation by ISG20 than those produced in cells expressing FTSJ3. Finally, we found that reverse-transcription of hypomethylated HIV-1 was impaired in T cel...
Nature Communications, 2015
The L protein of mononegaviruses harbours all catalytic activities for genome replication and tra... more The L protein of mononegaviruses harbours all catalytic activities for genome replication and transcription. It contains six conserved domains (CR-I to -VI; Fig. 1a). CR-III has been linked to polymerase and polyadenylation activity, CR-V to mRNA capping and CR-VI to cap methylation. However, how these activities are choreographed is poorly understood. Here we present the 2.2-Å X-ray structure and activities of CR-VI+, a portion of human Metapneumovirus L consisting of CR-VI and the poorly conserved region at its C terminus, the +domain. The CR-VI domain has a methyltransferase fold, which besides the typical S-adenosylmethionine-binding site (SAMP) also contains a novel pocket (NSP) that can accommodate a nucleoside. CR-VI lacks an obvious cap-binding site, and the SAMP-adjoining site holding the nucleotides undergoing methylation (SUBP) is unusually narrow because of the overhanging +domain. CR-VI+ sequentially methylates caps at their 2′O and N7 positions, and also displays nucle...
Collection Symposium Series, 2014
Nucleic acids symposium series, 1992
A convenient synthesis of a thymidine (T) nucleoside dimer (T-3'-CH2-O-NCH3-CH2-4'-T) 12 ... more A convenient synthesis of a thymidine (T) nucleoside dimer (T-3'-CH2-O-NCH3-CH2-4'-T) 12 has been accomplished via a nucleoside coupling reaction. An alternative synthesis of 3'-deoxy-3'-C-hydroxymethyl-thymidine is described. The new dimer and methodology is useful for the development of backbone-modified antisense oligonucleosides.
ChemInform, 2004
For Abstract see ChemInform Abstract in Full Text.