1FTD

5'-D(*CP*GP*CP*GP*AP*AP*TP*TP*CP*GP*CP*G)-3'-SYMMETRIC BIS-BENZIMIDAZOLE COMPLEX

1FTD の概要

• エントリーDOI: 10.2210/pdb1ftd/pdb
• 分子名称: DNA (5'-D(*CP*GP*CP*GP*AP*AP*TP*TP*CP*GP*CP*G)-3'), MAGNESIUM ION, [3-(4-{2'-[4-(3-DIMETHYLAMINO-PROPOXY)-PHENYL]-3H,3'H-[5,5']BIBENZOIMIDAZOLYL-2-YL}-PHENOXY)-PROPYL]-DIMETHYL-AMINE, ... (4 entities in total)
• 機能のキーワード: minor groove binding, dna
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 7939.83

構造登録者

Mann, J.,Baron, A.,Opoku-Boahen, Y.,Johansson, E.,Parkinson, G.,Kelland, L.R.,Neidle, S. (登録日: 2000-09-12, 公開日: 2001-02-26, 最終更新日: 2024-02-07)

主引用文献

Mann, J.,Baron, A.,Opoku-Boahen, Y.,Johansson, E.,Parkinson, G.,Kelland, L.R.,Neidle, S.
A new class of symmetric bisbenzimidazole-based DNA minor groove-binding agents showing antitumor activity.
J.Med.Chem., 44:138-144, 2001

PubMed Abstract: The synthesis and evaluation of the novel head-to-head bisbenzimidazole compound 2,2-bis[4'-(3' '-dimethylamino-1' '-propyloxy)phenyl]-5,5-bi-1H-benzimidazole is described. An X-ray crystallographic study of a complex with the DNA dodecanucleotide sequence d(CGCGAATTCGCG) shows the compound bound in the A/T minor groove region of a B-DNA duplex and that the head-to-head bisbenzimidazole motif hydrogen-bonds to the edges of all four consecutive A:T base pairs. The compound showed potent growth inhibition with a mean IC(50) across an ovarian carcinoma cell line panel of 0.31 microM, with no significant cross-resistance in two acquired cisplatin-resistant cell lines and a low level of cross-resistance in the P-glycoprotein overexpressing acquired doxorubicin-resistant cell line. Studies with the hollow fiber assay and in vivo tumor xenografts showed some evidence of antitumor activity.

PubMed: 11170623
DOI: 10.1021/jm000297b

実験手法

X-RAY DIFFRACTION (2 Å)