title: Discovery of G-quadruplex stabilizing ligands through direct ELISA of a one-bead-one-compound library.
abstract: We describe the identification of small-molecule G-quadruplex ligands using a direct ELISA screen of a one-bead-one-compound library of unnatural polyamides displayed on a branched linker with a biotin tag. This general purpose parallel screen for small molecule-oligonucleotide interactions was validated by surface plasmon resonance and ELISA of resynthesized compounds. Linear polyamides displayed similar rankings in their affinity for quadruplex as their branched counterparts. Quadruplex affinity as judged by these surface based techniques was a useful predictor of the ability of the ligands to stabilize the quadruplex to thermal unfolding in solution.
authors.affiliation: University Chemical Laboratory, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.
authors.forename: James E
authors.initials: JE
authors.lastname: Redman
authors.forename: Sylvain
authors.initials: S
authors.lastname: Ladame
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Reszka
authors.forename: Stephen
authors.initials: S
authors.lastname: Neidle
authors.forename: Shankar
authors.initials: S
authors.lastname: Balasubramanian
mesh_terms: D020650:Combinatorial Chemistry Techniques; D004247:DNA / Q000737:chemistry*; D004797:Enzyme-Linked Immunosorbent Assay; D031541:Fluorescence Resonance Energy Transfer; D054856:G-Quadruplexes; D006801:Humans; D008024:Ligands; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000737:chemistry; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D020349:Surface Plasmon Resonance
chemical_list: D008024:Ligands; D009842:Oligopeptides; D010455:Peptides; D004247:DNA; C085706:FLAG peptide