DNA interaction of the imidazole-containing lexitropsin ImPy: titration viscometric study in comparison to netropsin.
The imidazole (Im) containing lexitropsin ImPy related to netropsin (Nt) is a sequence reading DNA ligand which, in contrast to Nt, permits binding to a GC base pair. The ImPy induced DNA conformational changes differ significantly from those induced by Nt as monitored by titration viscometry, although interaction modes have also been resolved with boundaries at the same ligand to DNA phosphate ratio, r. Evidently ImPy covers similar binding sites (in the same sequence) as Nt for natural calf thymus DNA at r < 0.023. This result suggests that the preferred binding sites of ImPy are A tracts (cf. K.E.R. JBSD 9(1993) 973), in agreement with previous data. The respective DNA coil expansion, most probably caused by unbending (l.c.), is similar but smaller compared to the Nt-DNA interaction. These results again suggest that, at low r values, the van der Waals interaction in the narrowed minor groove of AT clusters provides a dominating energy contribution to ImPy binding. At r > 0.03 the DNA coil expansion increases to extremely high values in that r range where Nt binding (to mixed AT/GC sequences) induces no effect at all owing to steric hindrance with the amino group of guanine. On the basis of many quantitative results for the Nt-DNA systems these effects can be understood in terms of an unbending of intrinsic helix bends (l.c.). They are of considerable interest in connection with the ability of such compounds to influence the direction of the local regulatory relevant DNA curvature.
Reinert
K E
KE
Institute of Molecular Biology, Friedrich-Schiller-University, Jena, Germany.
Stutter
E
E
Zimmer
C
C
Lown
J W
JW
D000818:Animals; D001665:Binding Sites; D002417:Cattle; D004247:DNA / Q000737:chemistry*; D007093:Imidazoles / Q000737:chemistry; D008024:Ligands; D015394:Molecular Structure; D009429:Netropsin / Q000031:analogs & derivatives* / Q000737:chemistry; D017186:Titrimetry; D014783:Viscosity
D007093:Imidazoles; D008024:Ligands; C053654:lexitropsin; D009429:Netropsin; C029899:imidazole; D004247:DNA