NB‐506, an indolocarbazole topoisomerase I inhibitor, binds preferentially to triplex DNA

FEBS Letters

Ren, Jinsong²  Chaires, Jonathan B.²  Bailly, Christian¹ 

[1] Laboratoire de Pharmacologie Antitumorale du Centre Oscar Lambret, INSERM U-124, IRCL, Place de Verdun, 59045 Lille, France;Department of Biochemistry, University of Mississippi Medical Center, 2500 N. State St., Jackson, MS 39216-4505, USA

关键词: DNA;    RNA;    Intercalation;    Dialysis;    Anticancer drug;    Triplex DNA;   

DOI  :  10.1016/S0014-5793(00)01335-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown