Jean-Luc Décout

Bio: Jean-Luc Décout is an academic researcher from University of Grenoble. The author has contributed to research in topics: Neamine & Oligonucleotide. The author has an hindex of 27, co-authored 123 publications receiving 1995 citations. Previous affiliations of Jean-Luc Décout include Rega Institute for Medical Research & French Alternative Energies and Atomic Energy Commission.

Bacterial lipid membranes as promising targets to fight antimicrobial resistance, molecular foundations and illustration through the renewal of aminoglycoside antibiotics and emergence of amphiphilic aminoglycosides

Abstract: Hereunder, we highlight bacterial membrane anionic lipids as attractive targets in the design of antibacterial drugs which can be effective against both Gram-positive and Gram-negative resistant bacteria. In this approach, first, molecular foundations and structure–activity relationships are laid out for membrane-targeting drugs and drug candidates from the structure and physicochemical properties of the main membrane targets, describing, as well, the corresponding identified resistances. Second, this approach is illustrated by the history of the emergence of antibacterial and antifungal amphiphilic aminoglycosides (AAGs) which are active against Gram-positive and Gram-negative resistant bacteria. AAGs have resulted from intensive medicinal chemistry development of a group of old antibiotic drugs known as aminoglycosides (AGs), which target ribosomal RNA. The aforementioned AAG's are being used towards discovering new antibiotics which are less toxic and less susceptible to resistance. The recent results in the field of AAGs are described and discussed in terms of structure–activity relationships and mechanism of action.

New 7-Methylguanine Derivatives Targeting the Influenza Polymerase PB2 Cap-Binding Domain

Abstract: The heterotrimeric influenza virus polymerase performs replication and transcription of viral RNA in the nucleus of infected cells Transcription by "cap-snatching" requires that host-cell pre-mRNAs are bound via their 5' cap to the PB2 subunit Thus, the PB2 cap-binding site is potentially a good target for new antiviral drugs that will directly inhibit viral replication Docking studies using the structure of the PB2 cap-binding domain suggested that 7-alkylguanine derivatives substituted at position N-9 and N-2 could be good candidates Four series of 7,9-di- and 2,7,9-trialkyl guanine derivatives were synthesized and evaluated by an AlphaScreen assay in competition with a biotinylated cap analogue Three synthesized compounds display potent in vitro activity with IC50 values lower than 10 μM High-resolution X-ray structures of three inhibitors in complex with the H5N1 PB2 cap-binding domain confirmed the binding mode and provide detailed information for further compound optimization

RNA Targeting Therapeutics: Molecular Mechanisms of Antisense Oligonucleotides as a Therapeutic Platform

Abstract: Dramatic advances in understanding of the roles RNA plays in normal health and disease have greatly expanded over the past 10 years and have made it clear that scientists are only beginning to comprehend the biology of RNAs. It is likely that RNA will become an increasingly important target for therapeutic intervention; therefore, it is important to develop strategies for therapeutically modulating RNA function. Antisense oligonucleotides are perhaps the most direct therapeutic strategy to approach RNA. Antisense oligonucleotides are designed to bind to the target RNA by well-characterized Watson-Crick base pairing, and once bound to the target RNA, modulate its function through a variety of postbinding events. This review focuses on the molecular mechanisms by which antisense oligonucleotides can be designed to modulate RNA function in mammalian cells and how synthetic oligonucleotides behave in the body.