1ftd

[[Image:1ftd.gif|left|200px]]

|PDB= 1ftd |SIZE=350|CAPTION= <scene name='initialview01'>1ftd</scene>, resolution 2.&Aring;

|SITE=

|LIGAND= <scene name='pdbligand=DA:2&#39;-DEOXYADENOSINE-5&#39;-MONOPHOSPHATE'>DA</scene>, <scene name='pdbligand=DC:2&#39;-DEOXYCYTIDINE-5&#39;-MONOPHOSPHATE'>DC</scene>, <scene name='pdbligand=DG:2&#39;-DEOXYGUANOSINE-5&#39;-MONOPHOSPHATE'>DG</scene>, <scene name='pdbligand=DT:THYMIDINE-5&#39;-MONOPHOSPHATE'>DT</scene>, <scene name='pdbligand=E97:[3-(4-{2&#39;-[4-(3-DIMETHYLAMINO-PROPOXY)-PHENYL]-3H,3&#39;H-[5,5&#39;]BIBENZOIMIDAZOLYL-2-YL}-PHENOXY)-PROPYL]-DIMETHYL-AMINE'>E97</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>

|ACTIVITY=

|GENE=

|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ftd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ftd OCA], [http://www.ebi.ac.uk/pdbsum/1ftd PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1ftd RCSB]</span>

 

 

 

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.

 

1FTD is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FTD OCA].

 

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:[http://www.ncbi.nlm.nih.gov/pubmed/11170623 11170623]

[[Category: Protein complex]]

[[Category: Baron, A.]]

[[Category: Johansson, E.]]

[[Category: Kelland, L R.]]

[[Category: Mann, J.]]

[[Category: Neidle, S.]]

[[Category: Opoku-Boahen, Y.]]

[[Category: Parkinson, G.]]