Interaction of unfused tricyclic aromatic cations with DNA: A new class of intercalators

Journal Article · Tue Mar 07 04:00:00 EST 1989 · Biochemistry; (USA)

DOI:https://doi.org/10.1021/bi00431a005· OSTI ID:5645035

Wilson, W D; Tanious, F A; Watson, R A; Barton, H J; Strekowska, A; Harden, D B; Strekowski, L ^[1]

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1. Georgia State Univ., Atlanta (USA)

Unfused tricyclic aromatic ring systems 1-6 with one or two cationic side chains have been synthesized and their interactions with DNA and synthetic polymers probed with a variety of techniques. Molecular mechanics calculations indicate that the torsional angle between ring planes in the minimum energy conformation of the tricyclic molecules can range from 0{degree} to as high as 50{degree} depending on the type of rings and substituents. Viscometric titrations with linear and supercoiled DNA, linear dichroism, and NMR studies indicated that all compounds with torsional angles of approximately 20{degree} or less bind to DNA by intercalation. The more highly twisted intercalators caused significant perturbation of DNA structure. Unfused intercalators with twist angles of approximately 20{degree} have reduced binding constants, suggesting that they could not form an optimum interaction with the DNA base pairs. Unfused intercalators with twist less than 20{degree} formed strong complexes with DNA. The structures of these unfused intercalators are more analogous to typical groove-binding molecules, and an analysis of their interaction with DNA provides a better understanding of the subtle differences between intercalation and groove-binding modes for aromatic cations. The results indicate that intercalation and groove-binding modes should be viewed as two potential wells on a continuous energy surface. The results also suggest design strategies for intercalators that can optimally complement DNA base pair propeller twist or that can induce bends in DNA at the intercalation site.

• OSTI ID: 5645035
• Journal Information: Biochemistry; (USA), Journal Name: Biochemistry; (USA) Vol. 28:5; ISSN 0006-2960; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550601 -- Medicine-- Unsealed Radionuclides in Diagnostics
560300* -- Chemicals Metabolism & Toxicology
62 RADIOLOGY AND NUCLEAR MEDICINE
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
AROMATICS
BIOLOGICAL EFFECTS
BODY
CALVES
CATTLE
CHEMICAL REACTIONS
CHEMICAL SHIFT
CROSS-LINKING
DNA
DOMESTIC ANIMALS
LYMPHATIC SYSTEM
MAGNETIC RESONANCE
MAMMALS
NUCLEAR MAGNETIC RESONANCE
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
POLYMERIZATION
RESONANCE
RUMINANTS
THYMUS
VERTEBRATES
VISCOSITY