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RESEARCH PRODUCT
“One Ring to Bind Them All”—Part II: Identification of Promising G-Quadruplex Ligands by Screening of Cyclophane-Type Macrocycles
Aurore GuédinAnton GranzhanNicolas SaettelMarie-paule Teulade-fichouDavid MonchaudJean-louis Mergnysubject
lcsh:QH426-470Article SubjectHigh selectivityStructural diversityBiology010402 general chemistryRing (chemistry)G-quadruplexBioinformatics01 natural sciencesBiochemistrylcsh:Biochemistry03 medical and health scienceschemistry.chemical_compound[SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular Biology[SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biologylcsh:QD415-436Molecular Biology030304 developmental biology0303 health sciencesCombinatorial chemistry0104 chemical scienceslcsh:GeneticschemistryIdentification (biology)CyclophaneResearch Articledescription
A collection of 26 polyammonium cyclophane-type macrocycles with a large structural diversity has been screened for G-quadruplex recognition. A two-step selection procedure based on the FRET-melting assay was carried out enabling identification of macrocycles of high affinity (ΔT1/2up to30°C) and high selectivity for the human telomeric G-quadruplex. The four selected hits possess sophisticated architectures, more particularly the presence of a pendant side-arm as well as the existence of a particular topological arrangement appear to be strong determinants of quadruplex binding. These compounds are thus likely to create multiple contacts with the target that may be at the origin of their high selectivity, thereby suggesting that this class of macrocycles offers unique advantages for targeting G-quadruplex-DNA.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2010-01-29 | Journal of Nucleic Acids |