Tuning the DNA conformational perturbations induced by cytotoxic platinum-acridine bisintercalators: effect of metal cis/trans isomerism and DNA threading groups.
Four highly charged, water soluble platinum-acridine bisintercalating agents have been synthesized. Depending on the cis/trans isomerism of the metal and the nature of the acridine side chains, bisintercalation induces/stabilizes the classical Watson-Crick B-form or a non-B-form. Circular dichroism spectra and chemical footprinting experiments suggest that 4, the most active derivative in HL-60 cells, produces a structurally severely perturbed DNA with features of a Hoogsteen base-paired biopolymer.
Choudhury
Jayati Roy
JR
Department of Chemistry, Wake Forest University, Winston-Salem, NC 27109, USA.
Guddneppanavar
Rajsekhar
R
Saluta
Gilda
G
Kucera
Gregory L
GL
Bierbach
Ulrich
U
D000166:Acridines / Q000737:chemistry* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D002614:Chelating Agents / Q000737:chemistry*; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D018922:HL-60 Cells; D006801:Humans; D007364:Intercalating Agents / Q000737:chemistry* / Q000494:pharmacology; D009690:Nucleic Acid Conformation; D010984:Platinum; D011089:Polydeoxyribonucleotides / Q000737:chemistry; D012995:Solubility; D013237:Stereoisomerism; D014867:Water
D000166:Acridines; D000970:Antineoplastic Agents; D002614:Chelating Agents; D007364:Intercalating Agents; D011089:Polydeoxyribonucleotides; D014867:Water; C019530:poly(dC-dG); D010984:Platinum; D004247:DNA