NB-506, an indolocarbazole topoisomerase I inhibitor, binds preferentially to triplex DNA.
A novel competition dialysis method was used to study the structural selectivity of the nucleic acid binding of NB-506, a promising indolocarbazole anticancer agent. A pronounced preference for NB-506 binding to the DNA triplex poly [dA]:(poly[dT])(2) was observed among potential binding to 12 different nucleic acid structures and sequences. Structures included in the assay ranged from single-stranded DNA, through a variety of right-handed DNA duplexes, to multistranded triplex and tetraplex forms. RNA and left-handed Z DNA were also included in the assay. The preferential binding to triplex was confirmed by UV melting experiments. The novel and unexpected structural selectivity shown by NB-506 may arise from a complementary shape between its extended aromatic ring system and the planar triplex stack.
Ren
J
J
Department of Biochemistry, University of Mississippi Medical Center, 2500 N. State St., Jackson, MS 39216-4505, USA.
Bailly
C
C
Chaires
J B
JB
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism*; D001667:Binding, Competitive; D002227:Carbazoles / Q000737:chemistry / Q000378:metabolism*; D002417:Cattle; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004277:DNA, Single-Stranded / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D003956:Dialysis; D054856:G-Quadruplexes; D005960:Glucosides / Q000737:chemistry / Q000378:metabolism*; D006358:Hot Temperature; D007364:Intercalating Agents / Q000737:chemistry / Q000378:metabolism; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D013379:Substrate Specificity; D013816:Thermodynamics; D059004:Topoisomerase I Inhibitors; D014466:Ultraviolet Rays
D000970:Antineoplastic Agents; D002227:Carbazoles; D004277:DNA, Single-Stranded; D005960:Glucosides; D007364:Intercalating Agents; C092476:NB 506; D059004:Topoisomerase I Inhibitors; C051802:triplex DNA; D004247:DNA; D004264:DNA Topoisomerases, Type I