Footprinting studies on the sequence‐selective binding of pentamidine to DNA

Fox, Keith R.; Sansom, Clare; Stevens, Malcolm F. G.

doi:10.1016/0014-5793(90)81527-u

Cited by 49 publications

(36 citation statements)

References 12 publications

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“…the DNA within the A+T-rich minor groove, as had been previously suggested for pentamidine from footprinting studies (Fox et al, 1990). From an examination of these two structures, we have been able to establish a rational basis for the superior DNA-binding ability of propamidine as compared with pentamidine.…”

Section: Fig 2 the Y-oxapentamidine-d(cgcgaattcgcg) Complex (Left)mentioning

confidence: 52%

Crystal Structure of γ‐Oxapentamidine Complexed with d(CGCGAATTCGCG)₂

Nunn

Jenkins

Neidle

1994

European Journal of Biochemistry

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The crystal structure of the complex of γ‐oxapentamidine and the DNA dodecamer d(CGCGAATTCGCG)2 has been determined to a resolution of 0.22 nm and an R factor of 18.9%. The γ‐oxapentamidine ligand interacts with the dodecamer by classic minor groove binding via interactions within the Arich region of the minor groove. A chain of solvent molecules lies along the mouth of the minor groove on the outside of the bound ligand. The structural details of the complex are discussed and compared with the closely analogous complex with pentamidine bound to the same dodecamer [Edwards, K. J., Jenkins, T. C. & Neidle, S. (1992) Biochemistry 31, 7104–7109]. The amidinium groups of the ligand do not hydrogen bond to bases, but are in close contact with O4′ sugar ring atoms. This in part explains the reduced DNA binding affinity of this ligand compared to pentamidine.

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Section: Fig 2 the Y-oxapentamidine-d(cgcgaattcgcg) Complex (Left)mentioning

confidence: 52%

Crystal Structure of γ‐Oxapentamidine Complexed with d(CGCGAATTCGCG)₂

Nunn

Jenkins

Neidle

1994

European Journal of Biochemistry

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“…Diamidines such as pentamidine, 4',6-diamidino-2-phenylindole, and berenil have been shown to bind preferentially to A+T-rich regions in minor grooves of B-DNA without intercalating between base pairs (12,28,32,34,38). The preferential binding of diamidino compounds to A+T-rich regions is further confirmed by the disruption of A+T-rich kinetoplastic DNA in leishmania (7) and trypanosomes (33).…”

Section: Resultsmentioning

confidence: 93%

“…It has been suggested that these compounds interfere with nucleic acid synthesis and/or metabolism (16,40,44). Pentamidine and other diamidines, such as 4',6-diamidino-2-phenylindole and berenil, have been shown to bind to DNA and exhibit a preference for binding to A+T-rich regions in the minor groove of B-DNA (12,28,32,34,38). To assess their range of activity further and better understand the mechanism(s) of antimicrobial action, we examined the structure-activity relationships of pentamidine and 38 analogs of pentamidine in an in vitro assay against G. lamblia WB (ATCC 30957) and correlated the antigiardial activities of these dicationic molecules with their DNA-binding affinities.…”

mentioning

confidence: 99%

Structure-activity relationships of pentamidine analogs against Giardia lamblia and correlation of antigiardial activity with DNA-binding affinity

Bell

Cory

Fairley

et al. 1991

Antimicrob Agents Chemother

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1,5-Di(4-amidinophenoxy)pentane (pentamidine) and 38 analogs of pentamidine were screened for in vitro activity against the enteric protozoan Giardia lamblia WB (ATCC 30957). All compounds were active against G. lamblia as measured by a [methyl-3H]thymidine incorporation assay. Antigiardial activity varied widely, with 50% inhibitory concentrations (IC50s) ranging from 0.51 +/- 0.13 microM (mean +/- standard deviation) for the most active compound to over 100.0 microM for the least active compounds. The IC50 of the most potent antigiardial agent, 1,3-di(4-amidino-2-methoxyphenoxy)propane compared favorably with the IC50s of the compounds currently used to treat giardiasis, i.e., furazolidone (1.0 +/- 0.03 microM), metronidazole (2.1 +/- 0.80 microM), quinacrine HCl (0.03 +/- 0.02 microM), and tinidazole (0.78 +/- 0.48 microM). A mode of antigiardial activity for these compounds was suggested by the correlation observed between antigiardial activity and the binding of the compounds to calf thymus DNA and poly(dA).poly(dT).

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“…Because of their high sequence specificity, they are rarely used and often considered as poor footprinting reagents. They have been tested mostly against AT-specific ligands (7,21,37,38). We find that these enzymes can, under the right circumstances, yield extremely interesting complementary information in the case of non-strictly AT-specific ligands; in some ways they are particularly well adapted for footprinting lexitropsins.…”

Section: Discussionmentioning

confidence: 99%

DNA-sequence specific recognition by a thiazole analogue of netropsin: a comparative footprinting study

Plouvier¹,

Bailly²,

Houssin³

et al. 1991

Nucl Acids Res

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Four different footprinting techniques have been used to probe the DNA sequence selectivity of Thia-Net, a bis-cationic analogue of the minor groove binder netropsin in which the N-methylpyrrole moieties are replaced by thiazole groups. In Thia-Net the ring nitrogen atoms are directed into the minor groove where they could accept hydrogen bonds from the exocyclic 2-amino group of guanine. Three nucleases (DNAase 1, DNAase 11, and micrococcal nuclease) were employed to detect binding sites on the 160bp tyr T fragment obtained from plasmid pKMA-98, and further experiments were performed with 1 1 7mer and 253mer fragments cut out of the plasmid pBS. MPE-Fe(ll) was used to footprint binding sites on an EcoRI/Hindlll fragment from pBR322. Thia-Net binds to sites in the minor groove containing 4 or 5 base pairs which are predominantly composed of alternating A and T residues, but with significant acceptance of intrusive GC base pairs. Unlike the parent antibiotic netropsin, Thia-Net discriminates against homooligomeric runs of A and T. The evident preference of Thia-Net for AT-rich sites, despite its containing thiazole nitrogens capable of accepting GC sites by hydrogen bonding, supports the view that the biscationic nature of the ligand imposes a bias due to the electrostatic potential differences in the receptor which favour the ligand reading alternating AT sequences. INTRODUCTIONSequence-specific molecular recognition of DNA by proteins is central to the regulation of many cellular processes (1,2). Examination of the interaction between oligopeptides and DNA can be useful as a means of elucidating the structural basis for such selectivity. Moreover, studies of the interaction of oligopeptides with DNA have become increasingly important for

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Footprinting studies on the sequence‐selective binding of pentamidine to DNA

Cited by 49 publications

References 12 publications

Crystal Structure of γ‐Oxapentamidine Complexed with d(CGCGAATTCGCG)₂

Crystal Structure of γ‐Oxapentamidine Complexed with d(CGCGAATTCGCG)₂

Structure-activity relationships of pentamidine analogs against Giardia lamblia and correlation of antigiardial activity with DNA-binding affinity

DNA-sequence specific recognition by a thiazole analogue of netropsin: a comparative footprinting study

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Footprinting studies on the sequence‐selective binding of pentamidine to DNA

Cited by 49 publications

References 12 publications

Crystal Structure of γ‐Oxapentamidine Complexed with d(CGCGAATTCGCG)2

Crystal Structure of γ‐Oxapentamidine Complexed with d(CGCGAATTCGCG)2

Structure-activity relationships of pentamidine analogs against Giardia lamblia and correlation of antigiardial activity with DNA-binding affinity

DNA-sequence specific recognition by a thiazole analogue of netropsin: a comparative footprinting study

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Crystal Structure of γ‐Oxapentamidine Complexed with d(CGCGAATTCGCG)₂

Crystal Structure of γ‐Oxapentamidine Complexed with d(CGCGAATTCGCG)₂