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| | {{STRUCTURE_2gb9| PDB=2gb9 | SCENE= }} | | {{STRUCTURE_2gb9| PDB=2gb9 | SCENE= }} |
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| - | '''d(CGTACG)2 crosslinked bis-acridine complex'''
| + | ===d(CGTACG)2 crosslinked bis-acridine complex=== |
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| - | ==Overview==
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| - | Acridine-4-carboxamides form a class of known DNA mono-intercalating agents that exhibit cytotoxic activity against tumour cell lines due to their ability to inhibit topoisomerases. Previous studies of bis-acridine derivatives have yielded equivocal results regarding the minimum length of linker necessary between the two acridine chromophores to allow bis-intercalation of duplex DNA. We report here the 1.7 A resolution X-ray crystal structure of a six-carbon-linked bis(acridine-4-carboxamide) ligand bound to d(CGTACG)2 molecules by non-covalent duplex cross-linking. The asymmetric unit consists of one DNA duplex containing an intercalated acridine-4-carboxamide chromophore at each of the two CG steps. The other half of each ligand is bound to another DNA molecule in a symmetry-related manner, with the alkyl linker threading through the minor grooves. The two crystallographically independent ligand molecules adopt distinct side chain interactions, forming hydrogen bonds to either O6 or N7 on the major groove face of guanine, in contrast to the semi-disordered state of mono-intercalators bound to the same DNA molecule. The complex described here provides the first structural evidence for the non-covalent cross-linking of DNA by a small molecule ligand and suggests a possible explanation for the inconsistent behaviour of six-carbon linked bis-acridines in previous assays of DNA bis-intercalation.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_17145714}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 17145714 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_17145714}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Searcey, M.]] | | [[Category: Searcey, M.]] |
| | [[Category: Dna duplex crosslinking]] | | [[Category: Dna duplex crosslinking]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 04:54:35 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 10:01:14 2008'' |
Revision as of 07:01, 28 July 2008
Template:STRUCTURE 2gb9
d(CGTACG)2 crosslinked bis-acridine complex
Template:ABSTRACT PUBMED 17145714
About this Structure
Full crystallographic information is available from OCA.
Reference
X-ray crystallographic study of DNA duplex cross-linking: simultaneous binding to two d(CGTACG)2 molecules by a bis(9-aminoacridine-4-carboxamide) derivative., Hopcroft NH, Brogden AL, Searcey M, Cardin CJ, Nucleic Acids Res. 2006;34(22):6663-72. Epub 2006 Dec 1. PMID:17145714
Page seeded by OCA on Mon Jul 28 10:01:14 2008
