NDLI: Does irehdiamine kink DNA?

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Does irehdiamine kink DNA?

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Does irehdiamine kink DNA?

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Hogan, M. Crothers, D. M. Dattagupta, N.
Abstract	We report equilibrium, relaxation kinetic, and transient electric dichroism studies on the complex of the diamino steroid irehdiamine A with DNA. The results are consistent with a beta-kinked structure for the complex at saturation, with a kink in the DNA structure induced by a bound steroid every second base pair. The results that favor this hypothesis include an apparent length decrease of rod-like bacterial DNA molecules when only a small amount of drug is bound, followed by an apparent length increase at saturation. The limiting dichroism amplitude implies a substantial increase in the tilt of the bases relative to the orientation axis; at saturation the base UV transition moments are tilted about 31 degrees from the plane perpendicular to the orientation axis. Because of the direction of polarization of the 260-nm transition moments, the results indicate that the tilt of the bases must be predominantly in the short rather than the long axis of the base pair. The large hyperchroism of the complex is consistent with loss of base stacking, as required by a kinked structure. The kinetic results imply a bimolecular reaction mechanism, with a temperature-dependent association rate constant of roughly 10(8) M(-1) sec(-1), and a dissociation rate constant of about 5 x 10(3) sec(-1), nearly independent of temperature. The association activation energy and apparent reaction enthalpy vary from 12 to 22 kcal mol(-1); heat is absorbed on complex formation as expected for loss of base-stacking interactions. An anomalous result of the experiments is the larger apparent length increase (13%) exhibited by two eukaryotic DNAs, compared to 6% for three prokaryotic DNAs. Differences were also observed in the kinetic properties of the complexes.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	9
Volume Number	75
Language	English
Publisher	National Academy of Sciences
Publisher Date	1978-12-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	DNA Pregnenes Pharmacology Binding Sites Diamines Kinetics Nucleic Acid Conformation Drug Effects Poly DA-dT Spectrum Analysis Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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