Skip to Main content Skip to Navigation
Theses

Synthèse et utilisation de mimes de quadruplexes pour l'évaluation de ligands

Abstract : Synthesis and use of constrained quadruplexe mimic for the ligand evaluation It has now been shown that single stranded DNA can fold into hairpin, triplex, i-motif and G-quadruplexe structures containing non canonical base pairing. In particular quadruplex structures (G-quadruplexes and i-motif) have generated interest because the formation is considered to have important consequences at the cellular level (telomere maintenance, oncogene activation…). Therefore, the design of small molecules (ligands) targeting quadruplexes is under development, in particular to obtain anticancerous molecules. Nevertheless G-quadruplexes exhibit a wide structural polymorphism (different kind of loop, strand orientation, number of strands) making investigation of ligand tricky. In this context, we have developed a new concept called 'Template Assisted Synthesis of Quadruplex' (TASQ) with aim to constrain the G-quadruplex in a single conformation which enables the study of the interactions of ligand more specifically for a single topology. In the first part of this manuscript, we describe studies by using surface plasmon resonance (SPR) of metal complexes as G-quadruplex ligands. The investigation was performed using a first parallel G-quadruplex as model to interact with two kinds of metal complexes: metalloporphyrins and salphen. The second part of the manuscript reports the work concerning the synthesis of antiparallel quadruplexes. The strategy is based on the use of a peptide scaffold in which the suitable oligonucleotide sequences are anchored with specific orientation. For this purpose two compatible chemistries are used (1,3 dipolar Huisgen cycloaddition and oxime ligation). Three kinds of antiparallel quadruplexe mimics have been investigated: i-motif, tetramolecular G-quadruplexes and loop-constrained G-quadruplexes.
Document type :
Theses
Complete list of metadatas

Cited literature [186 references]  Display  Hide  Download

https://tel.archives-ouvertes.fr/tel-00824972
Contributor : Abes Star :  Contact
Submitted on : Wednesday, May 22, 2013 - 4:22:43 PM
Last modification on : Friday, November 6, 2020 - 3:49:54 AM
Long-term archiving on: : Friday, August 23, 2013 - 4:13:20 AM

File

31103_BONNET_2012_archivage.pd...
Version validated by the jury (STAR)

Identifiers

  • HAL Id : tel-00824972, version 1

Collections

Citation

Romaric Bonnet. Synthèse et utilisation de mimes de quadruplexes pour l'évaluation de ligands. Sciences agricoles. Université de Grenoble, 2012. Français. ⟨NNT : 2012GRENV069⟩. ⟨tel-00824972⟩

Share

Metrics

Record views

662

Files downloads

809