Chemistry of RNAs, Nucleosides, Peptides and Heterocycles

 

Team Composition

Mélanie Etheve-Quelquejeu, Pr

Permanent Staff

E. Braud, MCU, HDR
H. Chen, MCU, HDR
C. Garbay, PRem
L. Iannazzo, CR

Non Permanent Staff

K. Bartosik, Post-doc
S. Leprevost, ASI

PhD Students

Yusif Afandizada
Flavie Bouchet
Dylan Coelho
Camelia Kitoun
Louna Mossino
Saidbakhrom Saidjalolov

 

 

 

 

Our team is specialized in chemistry of nucleosides, nucleotides, peptides and heterocycles, which is used to generate molecules with desired physical or biological properties in order to better understand or inhibit biological processes. More recently, the team has reinforced is expertise in chemistry of nucleic acids to obtain synthetic RNAs and has acquired new expertise in β-lactamine chemistry. The molecules and biomolecules synthesized are used i) to explore the catalytic mechanism of transferases involved in the cell wall synthesis of bacteria  ii) to study transferases involved in epitranscriptomic events, iii) as tools for structural studies of enzymes. The different projects are presented below :

Chemistry of RNAs :

Development of new methodologies for post-functionalization of RNAs. Using our methodologies, we were able to synthesized :

Peptidyl-RNA conjugates for the study of FmhB of Staphyloccocus Aureus

Stable aminoacyl-tRNA analogues to explore non ribosomal peptide synthesis processes.

RNA-SAM cofactor conjugates to study  m6A-RNA methyltransferases.

– Development of Nanospectroscopy for mapping RNA profile in Tumor-educated blood platelets.
the chemistry of RNA

 

 

 

Chemistry of Peptides

We  synthezise peptidoglycan fragments to study L,D- transpeptidases enzymes involved in cell wall synthesis of Mycobacterium Tuberculosis.

 

Chemistry of Heterocycles

Development of new chemistry for the synthesis of carbapenem or avibactam analogues in order to inhibit or study the cell wall synthesis of bacteria. Development of selective inhibitors of FAK kinase is also one of our current projects.

All of these projects are at the interface between chemistry and biology and benefit from collaboration at the local, national and international levels.

1. C. Kitoun, M. Etheve-Quelquejeu, L. Iannazzo & al. Phosphine-Mediated Bioconjugation of 3’-end of RNA,  Org. Lett. 2020, DOI:10.1021/acs.orglett.0c02982.

2. F. Bouchet, H. Atze & al. Diazabicyclooctane functionalization for inhibition of β-lactamases from enterobacteria, Journal of Medicinal Chemistry,  2020, 63, 10, 5257–5273  https://doi.org/10.1021/acs.jmedchem.9b02125

3. C. Atdjian, L. Iannazzo, E. Braud & al. Synthesis of SAM-adenosine conjugates for the study of m6A-RNA methyltransferases Eur. J. Org. Chem., 2018, 4411-4425.

4. Fonvielle M., Bouhss A., L. Iannazzo & al. Synthesis of lipid-carbohydrate-peptidyl-RNA conjugates to explore the limits imposed by the substrate specificity of cell wall enzymes on the acquisition of drug resistance. Chem. Eur. J., 2018, 24:14911-14915.

5. L. Iannazzo, M. Fonvielle, E. Braud & al. Synthesis of tRNA analogues containing a terminal ribose locked in the South conformation to study tRNA-dependent enzymes  Org. Biomol. Chem., 2018, 16, 1903 – 1911
6. M. Fonvielle, N. Sakkas, L. Iannazzo & al. Electrophilic RNA for Peptidyl-RNA Synthesis and Site-Specific Cross-Linking with tRNA-Binding Enzymes. Angewandte Chem., 2016, 55, 13553–13557.

Chemistry of RNAs, Nucleosides, Peptides and Heterocycles

Team composition

Non Permanent Staff

K. Bartosik, Post-doc

PhD Students

Li Bo
Flavie Bouchet
Dylan Coelho
Camelia Kitoun
Saidbakhrom Saidjalolov

Our team is specialized in chemistry of nucleosides, nucleotides, peptides and heterocycles, which is used to generate molecules with desired physical or biological properties in order to better understand or inhibit biological processes. More recently, the team has reinforced is expertise in chemistry of nucleic acids to obtain synthetic RNAs and has acquired new expertise in β-lactamine chemistry. The molecules and biomolecules synthesized are used i) to explore the catalytic mechanism of transferases involved in the cell wall synthesis of bacteria  ii) to study transferases involved in epitranscriptomic events, iii) as tools for structural studies of enzymes. The different projects are presented below :

Chemistry of RNAs :

Development of new methodologies for post-functionalization of RNAs. Using our methodologies, we were able to synthesized :

Peptidyl-RNA conjugates for the study of FmhB of Staphyloccocus Aureus

Stable aminoacyl-tRNA analogues to explore non ribosomal peptide synthesis processes.

RNA-SAM cofactor conjugates to study  m6A-RNA methyltransferases.

– Development of Nanospectroscopy for mapping RNA profile in Tumor-educated blood platelets.
the chemistry of RNA

 

 

 

Chemistry of Peptides

We  synthezise peptidoglycan fragments to study L,D- transpeptidases enzymes involved in cell wall synthesis of Mycobacterium Tuberculosis.

 

Chemistry of Heterocycles

Development of new chemistry for the synthesis of carbapenem or avibactam analogues in order to inhibit or study the cell wall synthesis of bacteria. Development of selective inhibitors of FAK kinase is also one of our current projects.

All of these projects are at the interface between chemistry and biology and benefit from collaboration at the local, national and international levels.

1. C. Atdjian, L. Iannazzo, E. Braud & al. Synthesis of SAM-adenosine conjugates for the study of m6A-RNA methyltransferases Eur. J. Org. Chem., 2018, 4411-4425.
2. Fonvielle M., Bouhss A., L. Iannazzo & al. Synthesis of lipid-carbohydrate-peptidyl-RNA conjugates to explore the limits imposed by the substrate specificity of cell wall enzymes on the acquisition of drug resistance. Chem. Eur. J., 2018, 24:14911-14915.
3. Z. Edoo, L. Iannazzo et al. Synthesis of avibactam derivatives and activity on β-lactamases and peptidoglycan biosynthesis enzymes of mycobacteria. Beilstein J. Chem. Eur. J., 2018, 24, 8081-80-86.
4. E. Yen-Pon, B. Li & al. Structure-based design, synthesis and characterization of the first irreversible inhibitor of Focal Adhesion Kinase Curr. ACS Chem. Biol., 2018, doi: 10.1021/acschembio.8b00250
5. L. Iannazzo, M. Fonvielle, E. Braud & al. Synthesis of tRNA analogues containing a terminal ribose locked in the South conformation to study tRNA-dependent enzymes  Org. Biomol. Chem., 2018, 16, 1903 – 1911
6. M. Fonvielle, N. Sakkas, L. Iannazzo & al. Electrophilic RNA for Peptidyl-RNA Synthesis and Site-Specific Cross-Linking with tRNA-Binding Enzymes. Angewandte Chem., 2016, 55, 13553–13557.