BENA435, a new cell-permeant photoactivated green fluorescent DNA probe.
N'-(2,8-Dimethoxy-12-methyl-dibenzo [c,h] [1,5] naphthyridin-6-yl)-N,N-dimethyl-propane-1,3-diamine (BENA435) is a new cell-membrane permeant DNA dye with absorption/emission maxima in complex with DNA at 435 and 484 nm. This new reagent is unrelated to known DNA dyes, and shows a distinct preference to bind double-stranded DNA over RNA. Hydrodynamic studies suggest that BENA435 intercalates between the opposite DNA strands. BENA435 fluoresces much stronger when bound to dA/dT rather than dG/dC homopolymers. We evaluated 14 related dibenzonaphthyridine derivatives and found BENA435 to be superior in its in vivo DNA-binding properties. Molecular modelling was used to develop a model of BENA435 intercalation between base pairs of a DNA helix. BENA435 fluorescence in the nuclei of cells increases upon illumination, suggesting photoactivation. BENA435 represents thus the first known cell-permeant photoactivated DNA-binding dye.
Erve
Alexandra
A
Inserm, U366, DRDC/CS CEA-Grenoble, 17, rue des Martyrs, F-38054, Grenoble, cedex 9 France.
Saoudi
Yasmina
Y
Thirot
Sylvie
S
Guetta-Landras
Corinne
C
Florent
Jean-Claude
JC
Nguyen
Chi-Hung
CH
Grierson
David S
DS
Popov
Andrei V
AV
D000818:Animals; D002463:Cell Membrane Permeability; D002467:Cell Nucleus / Q000737:chemistry; D002478:Cells, Cultured; D003116:Color; D004247:DNA / Q000032:analysis* / Q000737:chemistry; D015342:DNA Probes / Q000737:chemistry* / Q000378:metabolism; D005456:Fluorescent Dyes / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007399:Interphase; D008027:Light; D051379:Mice; D008958:Models, Molecular; D009287:Naphthyridines / Q000737:chemistry* / Q000378:metabolism; D011067:Poly dA-dT / Q000032:analysis; D011089:Polydeoxyribonucleotides / Q000032:analysis; D012313:RNA / Q000032:analysis; D013329:Structure-Activity Relationship; D014981:Xenopus
D015342:DNA Probes; D005456:Fluorescent Dyes; C509332:N'-(2,8-dimethoxy-12-methyldibenzo(c,h)(1,5)naphthyridin-6-yl)-N,N-dimethylpropane-1,3-diamine; D009287:Naphthyridines; D011089:Polydeoxyribonucleotides; D011067:Poly dA-dT; C019530:poly(dC-dG); D012313:RNA; D004247:DNA