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Template‐Mediated Stabilization of a DNA G‐Quadruplex formed in the HIV‐1 Promoter and Comparative Binding Studies
Author(s) -
Bonnat Laureen,
Bar Laure,
Génnaro Béatrice,
Bonnet Hugues,
Jarjayes Olivier,
Thomas Fabrice,
Dejeu Jérôme,
Defrancq Eric,
Lavergne Thomas
Publication year - 2017
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.201700417
Subject(s) - oligonucleotide , circular dichroism , chemistry , antiparallel (mathematics) , click chemistry , g quadruplex , surface plasmon resonance , stereochemistry , dna , integrase , biophysics , combinatorial chemistry , biochemistry , biology , materials science , nanotechnology , physics , quantum mechanics , magnetic field , nanoparticle
G‐rich DNA oligonucleotides derived from the promoter region of the HIV‐1 long terminal repeat (LTR) were assembled onto an addressable cyclopeptide platform through sequential oxime ligation, a thiol‐iodoacetamide SN2 reaction, and copper‐catalyzed azide–alkyne cycloaddition reactions. The resulting conjugate was shown to fold into a highly stable antiparallel G4 architecture as demonstrated by UV, circular dichroism (CD), and NMR spectroscopic analysis. The binding affinities of six state‐of‐the‐art G4‐binding ligands toward the HIV‐G4 structure were compared to those obtained with a telomeric G4 structure and a hairpin structure. Surface plasmon resonance binding analysis provides new insights into the binding mode of broadly exploited G4 chemical probes and further suggests that potent and selective recognition of viral G4 structures of functional significance might be achieved.