1ftd
From Proteopedia
(New page: 200px<br /><applet load="1ftd" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ftd, resolution 2.Å" /> '''5'-D(*CP*GP*CP*GP*AP*A...) |
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| - | [[Image:1ftd.gif|left|200px]]<br /><applet load="1ftd" size=" | + | [[Image:1ftd.gif|left|200px]]<br /><applet load="1ftd" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1ftd, resolution 2.Å" /> | caption="1ftd, resolution 2.Å" /> | ||
'''5'-D(*CP*GP*CP*GP*AP*AP*TP*TP*CP*GP*CP*G)-3'-SYMMETRIC BIS-BENZIMIDAZOLE COMPLEX'''<br /> | '''5'-D(*CP*GP*CP*GP*AP*AP*TP*TP*CP*GP*CP*G)-3'-SYMMETRIC BIS-BENZIMIDAZOLE COMPLEX'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The synthesis and evaluation of the novel head-to-head bisbenzimidazole | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1FTD is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with MG and E97 as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1FTD is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=E97:'>E97</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FTD OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Baron, A.]] | [[Category: Baron, A.]] | ||
[[Category: Johansson, E.]] | [[Category: Johansson, E.]] | ||
| - | [[Category: Kelland, L | + | [[Category: Kelland, L R.]] |
[[Category: Mann, J.]] | [[Category: Mann, J.]] | ||
[[Category: Neidle, S.]] | [[Category: Neidle, S.]] | ||
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[[Category: minor groove binding]] | [[Category: minor groove binding]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:42:25 2008'' |
Revision as of 10:42, 21 February 2008
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5'-D(*CP*GP*CP*GP*AP*AP*TP*TP*CP*GP*CP*G)-3'-SYMMETRIC BIS-BENZIMIDAZOLE COMPLEX
Overview
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.
About this Structure
1FTD is a Protein complex structure of sequences from [1] with and as ligands. Full crystallographic information is available from OCA.
Reference
A new class of symmetric bisbenzimidazole-based DNA minor groove-binding agents showing antitumor activity., Mann J, Baron A, Opoku-Boahen Y, Johansson E, Parkinson G, Kelland LR, Neidle S, J Med Chem. 2001 Jan 18;44(2):138-44. PMID:11170623
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