1ftd: Difference between revisions

Line 1:

[[Image:1ftd.gif|left|200px]]<br /><applet load="1ftd" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

[[Image:1ftd.gif|left|200px]]<br /><applet load="1ftd" size="350" color="white" frame="true" align="right" spinBox="true"

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 />

==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.

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 [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://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1FTD OCA].

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==

Line 14:

[[Category: Baron, A.]]

[[Category: Johansson, E.]]

[[Category: Kelland, L.R.]]

[[Category: Kelland, L R.]]

[[Category: Mann, J.]]

[[Category: Neidle, S.]]

Line 23:

[[Category: minor groove binding]]

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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:42:25 2008''

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@@ Line 1: / Line 1: @@
-[[Image:1ftd.gif|left|200px]]<br /><applet load="1ftd" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1ftd.gif|left|200px]]<br /><applet load="1ftd" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1ftd, resolution 2.&Aring;" />
 '''5'-D(*CP*GP*CP*GP*AP*AP*TP*TP*CP*GP*CP*G)-3'-SYMMETRIC BIS-BENZIMIDAZOLE COMPLEX'''<br />
 ==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.
+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==
-FTD 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1FTD OCA].
+FTD 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==
@@ Line 14: / Line 14: @@
 [[Category: Baron, A.]]
 [[Category: Johansson, E.]]
-[[Category: Kelland, L.R.]]
+[[Category: Kelland, L R.]]
 [[Category: Mann, J.]]
 [[Category: Neidle, S.]]
@@ Line 23: / Line 23: @@
 [[Category: minor groove binding]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sun Nov 25 00:20:14 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:42:25 2008''