R. Wartell, J. E. Larson, R. Wells
Nov 10, 1974
Citations
3
Influential Citations
219
Citations
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Journal
The Journal of biological chemistry
Abstract
Abstract The binding of netropsin to 31 different natural and biosynthetic DNAs, DNA-RNA hybrids, and RNAs was studied in order to delineate the nucleic acid structural features necessary for binding. The measurements employed were spectral titrations, analytical density gradient centrifugation, thermal denaturation, equilibrium dialysis, and inhibition of in vitro replication and in vitro transcription. The major conclusions are: (a) in 0.1 m or higher salt concentrations, netropsin has a marked specificity for DNAs which contain A-T (or I-C) pairs. It binds tightly to two DNAs which contain only A-T pairs and to two DNAs which contain only I-C pairs. However, no measurable binding was found for two DNAs which contain only G-C pairs. (b) Netropsin's inability to bind to G-C paired regions is a consequence of the 2-amino group of guanine. (c) Netropsin is specific for duplex DNA; no binding was observed to five single-stranded DNAs, three helical RNAs, or two of the three DNA-RNA hybrids studied. (d) Netropsin binds to DNA by a nonintercalating mechanism, since it does not cause unwinding of supercoiled DNA. (e) Netropsin inhibits in vitro DNA and RNA synthesis by binding to the template or to the primer, or to both. (f) The closest distance between bound netropsin molecules is three base pairs. A molecular model for netropsin binding in the minor groove of DNA is proposed.