Premium
Templated Formation of Discrete RNA and DNA:RNA Hybrid G‐Quadruplexes and Their Interactions with Targeting Ligands
Author(s) -
Bonnat Laureen,
Dejeu Jérôme,
Bonnet Hugues,
Génnaro Béatrice,
Jarjayes Olivier,
Thomas Fabrice,
Lavergne Thomas,
Defrancq Eric
Publication year - 2016
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201504351
Subject(s) - rna , dna , oligonucleotide , antiparallel (mathematics) , chemistry , ribozyme , g quadruplex , combinatorial chemistry , circular dichroism , surface plasmon resonance , stereochemistry , nanotechnology , biochemistry , materials science , gene , physics , quantum mechanics , magnetic field , nanoparticle
G‐rich RNA and DNA oligonucleotides derived from the human telomeric sequence were assembled onto addressable cyclopeptide platforms through oxime ligations and copper‐catalyzed azide‐alkyne cycloaddition (CuAAc) reactions. The resulting conjugates were able to fold into highly stable RNA and DNA:RNA hybrid G‐quadruplex (G4) architectures as demonstrated by UV, circular dichroism (CD), and NMR spectroscopic analysis. Whereas rationally designed parallel RNA and DNA:RNA hybrid G4 topologies could be obtained, we could not force the formation of an antiparallel RNA G4 structure, thus supporting the idea that this topology is strongly disfavored. The binding affinities of four representative G4 ligands toward the discrete RNA and DNA:RNA hybrid G4 topologies were compared to the one obtained with the corresponding DNA G4 structure. Surface plasmon resonance (SPR) binding analysis suggests that the accessibility to G4 recognition elements is different among the three structures and supports the idea that G4 ligands might be shaped to achieve structure selectivity in a biological context.