Template-Mediated Stabilization of a DNA G-Quadruplex formed in the HIV-1 Promoter and Comparative Binding Studies

: 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.