DNA binding by analogues of the bifunctional intercalator TANDEM.
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.
Hampshire
Andrew J
AJ
School of Biological Sciences, University of Southampton, UK.
Rusling
David A
DA
Bryan
Stephanie
S
Paumier
David
D
Dawson
Simon J
SJ
Malkinson
John P
JP
Searcey
Mark
M
Fox
Keith R
KR
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
D007364:Intercalating Agents; D009281:Naphthalenes; D011810:Quinoxalines; C031721:naphthalene; C017738:TANDEM (quinoxaline); D004247:DNA; D003850:Deoxyribonuclease I; D014633:Valine; D008239:Lysine