title: Unexpected DNA affinity and sequence selectivity through core rigidity in guanidinium-based minor groove binders.
abstract: In this paper we report the design and biophysical evaluation of novel rigid-core symmetric and asymmetric dicationic DNA binders containing 9H-fluorene and 9,10-dihydroanthracene cores as well as the synthesis of one of these fluorene derivatives. First, the affinity toward particular DNA sequences of these compounds and flexible core derivatives was evaluated by means of surface plasmon resonance and thermal denaturation experiments finding that the position of the cations significantly influence the binding strength. Then their affinity and mode of binding were further studied by performing circular dichroism and UV studies and the results obtained were rationalized by means of DFT calculations. We found that the fluorene derivatives prepared have the ability to bind to the minor groove of certain DNA sequences and intercalate to others, whereas the dihydroanthracene compounds bind via intercalation to all the DNA sequences studied here.
authors.affiliation: School of Chemistry, Trinity College Dublin , Dublin 2, Ireland.
authors.forename: Padraic S
authors.initials: PS
authors.lastname: Nagle
authors.forename: Caitriona
authors.initials: C
authors.lastname: McKeever
authors.forename: Fernando
authors.initials: F
authors.lastname: Rodriguez
authors.forename: Binh
authors.initials: B
authors.lastname: Nguyen
authors.forename: W David
authors.initials: WD
authors.lastname: Wilson
authors.forename: Isabel
authors.initials: I
authors.lastname: Rozas
mesh_terms: D000873:Anthracenes / Q000737:chemistry / Q000378:metabolism; D001483:Base Sequence; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015195:Drug Design; D005449:Fluorenes / Q000737:chemistry / Q000378:metabolism; D019791:Guanidine / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D013379:Substrate Specificity; D044366:Transition Temperature
chemical_list: D000873:Anthracenes; D005449:Fluorenes; C041509:fluorene; D004247:DNA; C034020:anthracene; D019791:Guanidine