title: DNA binding by analogues of the bifunctional intercalator TANDEM.
abstract: We have used DNase I footprinting to study the binding strength and DNA sequence selectivity of novel derivatives of the quinoxaline bis-intercalator TANDEM. Replacing the valine residues in the cyclic octadepsipeptide with lysines does not affect the selectivity for TpA but leads to a 50-fold increase in affinity. In contrast, replacing both of the quinoxaline chromophores with naphthalene rings abolishes binding, while changing a single ring decreases the affinity, and footprints are observed at only the best binding sites (especially TATATA). By using fragments with different lengths of [(AT) n ], we demonstrate that these ligands bind best to the center of the longer (AT) n tracts.
authors.affiliation: School of Biological Sciences, University of Southampton, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Hampshire
authors.forename: David A
authors.initials: DA
authors.lastname: Rusling
authors.forename: Stephanie
authors.initials: S
authors.lastname: Bryan
authors.forename: David
authors.initials: D
authors.lastname: Paumier
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Dawson
authors.forename: John P
authors.initials: JP
authors.lastname: Malkinson
authors.forename: Mark
authors.initials: M
authors.lastname: Searcey
authors.forename: Keith R
authors.initials: KR
authors.lastname: Fox
mesh_terms: D001665:Binding Sites; D004247:DNA / Q000737:chemistry*; D018983:DNA Footprinting; D003850:Deoxyribonuclease I / Q000378:metabolism; D007364:Intercalating Agents / Q000737:chemistry*; D008239:Lysine / Q000737:chemistry; D008958:Models, Molecular; D009281:Naphthalenes / Q000737:chemistry; D011810:Quinoxalines / Q000737:chemistry; D014633:Valine / Q000737:chemistry
chemical_list: D007364:Intercalating Agents; D009281:Naphthalenes; D011810:Quinoxalines; C031721:naphthalene; C017738:TANDEM (quinoxaline); D004247:DNA; D003850:Deoxyribonuclease I; D014633:Valine; D008239:Lysine